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array:24 [ "pii" => "S1807593222019263" "issn" => "18075932" "doi" => "10.1590/S1807-59322011001200021" "estado" => "S300" "fechaPublicacion" => "2011-12-01" "aid" => "1926" "copyright" => "CLINICS" "copyrightAnyo" => "2011" "documento" => "article" "crossmark" => 0 "licencia" => "https://creativecommons.org/licenses/by-nc/3.0/" "subdocumento" => "rev" "cita" => "Clinics. 2011;66:2133-9" "abierto" => array:3 [ "ES" => true "ES2" => true "LATM" => true ] "gratuito" => true "lecturas" => array:1 [ "total" => 0 ] "itemSiguiente" => array:19 [ "pii" => "S1807593222019275" "issn" => "18075932" "doi" => "10.1590/S1807-59322011001200022" "estado" => "S300" "fechaPublicacion" => "2011-12-01" "aid" => "1927" "copyright" => "CLINICS" "documento" => "article" "crossmark" => 0 "licencia" => "https://creativecommons.org/licenses/by-nc/3.0/" "subdocumento" => "rev" "cita" => "Clinics. 2011;66:2141-9" "abierto" => array:3 [ "ES" => true "ES2" => true "LATM" => true ] "gratuito" => true "lecturas" => array:1 [ "total" => 0 ] "en" => array:11 [ "idiomaDefecto" => true "cabecera" => "<span class="elsevierStyleTextfn">REVIEW</span>" "titulo" => "Should we definitively abandon prophylaxis for patent ductus arteriosus in preterm new-borns?" "tienePdf" => "en" "tieneTextoCompleto" => "en" "tieneResumen" => "en" "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "2141" "paginaFinal" => "2149" ] ] "contieneResumen" => array:1 [ "en" => true ] "contieneTextoCompleto" => array:1 [ "en" => true ] "contienePdf" => array:1 [ "en" => true ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "Vassilios Fanos, Michele Pusceddu, Angelica Dessì, Maria Antonietta Marcialis" "autores" => array:4 [ 0 => array:2 [ "nombre" => "Vassilios" "apellidos" => "Fanos" ] 1 => array:2 [ "nombre" => "Michele" "apellidos" => "Pusceddu" ] 2 => array:2 [ "nombre" => "Angelica" "apellidos" => "Dessì" ] 3 => array:2 [ "nombre" => "Maria Antonietta" "apellidos" => "Marcialis" ] ] ] ] ] "idiomaDefecto" => "en" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S1807593222019275?idApp=UINPBA00004N" "url" => "/18075932/0000006600000012/v1_202212011437/S1807593222019275/v1_202212011437/en/main.assets" ] "itemAnterior" => array:19 [ "pii" => "S1807593222019251" "issn" => "18075932" "doi" => "10.1590/S1807-59322011001200020" "estado" => "S300" "fechaPublicacion" => "2011-12-01" "aid" => "1925" "copyright" => "CLINICS" "documento" => "article" "crossmark" => 0 "licencia" => "https://creativecommons.org/licenses/by-nc/3.0/" "subdocumento" => "fla" "cita" => "Clinics. 2011;66:2125-32" "abierto" => array:3 [ "ES" => true "ES2" => true "LATM" => true ] "gratuito" => true "lecturas" => array:1 [ "total" => 0 ] "en" => array:12 [ "idiomaDefecto" => true "cabecera" => "<span class="elsevierStyleTextfn">BASIC RESEARCH</span>" "titulo" => "The effects of heated vegetable oils on blood pressure in rats" "tienePdf" => "en" "tieneTextoCompleto" => "en" "tieneResumen" => "en" "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "2125" "paginaFinal" => "2132" ] ] "contieneResumen" => array:1 [ "en" => true ] "contieneTextoCompleto" => array:1 [ "en" => true ] "contienePdf" => array:1 [ "en" => true ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:7 [ "identificador" => "fig1" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 365 "Ancho" => 537 "Tamanyo" => 25756 ] ] "descripcion" => array:1 [ "en" => "<p id="spara10" class="elsevierStyleSimplePara elsevierViewall">Changes in blood pressure after 24 weeks of feeding with a basal diet (control) or chow amended with one of the following oils: fresh palm oil (FPO); palm oil that was heated once (1HPO), twice (2HPO), five times (5HPO), or ten times (10HPO); fresh soy oil (FSO); or soy oil that was heated once (1HSO), twice (2HSO), five times (5HSO), or ten times (10HSO). The results are the means ± SEM <span class="elsevierStyleBold">(n = 10)</span>. Significant difference (<span class="elsevierStyleItalic">p</span><0.05) versus the <span class="elsevierStyleBold"><span class="elsevierStyleSup">∗</span></span>control, <span class="elsevierStyleBold"><span class="elsevierStyleSup">#</span></span>fresh oil group, <span class="elsevierStyleBold"><span class="elsevierStyleSup">§</span></span>once-heated-oil group, or <span class="elsevierStyleBold"><span class="elsevierStyleSup">£</span></span>twice-heated-oil group. <span class="elsevierStyleBold"><span class="elsevierStyleSup">+</span></span>Significant difference (<span class="elsevierStyleItalic">p</span><0.05) between the palm and soy oil groups. The data are expressed as percentage based on baseline values.</p>" ] ] ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "Kamsiah Jaarin, Mohd Rais Mustafa, Xin-Fang Leong" "autores" => array:3 [ 0 => array:2 [ "nombre" => "Kamsiah" "apellidos" => "Jaarin" ] 1 => array:2 [ "nombre" => "Mohd Rais" "apellidos" => "Mustafa" ] 2 => array:2 [ "nombre" => "Xin-Fang" "apellidos" => "Leong" ] ] ] ] ] "idiomaDefecto" => "en" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S1807593222019251?idApp=UINPBA00004N" "url" => "/18075932/0000006600000012/v1_202212011437/S1807593222019251/v1_202212011437/en/main.assets" ] "en" => array:19 [ "idiomaDefecto" => true "cabecera" => "<span class="elsevierStyleTextfn">REVIEW</span>" "titulo" => "The effects of dietary supplementation with <span class="elsevierStyleItalic">Agaricales</span> mushrooms and other medicinal fungi on breast cancer: Evidence-based medicine" "tieneTextoCompleto" => true "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "2133" "paginaFinal" => "2139" ] ] "autores" => array:1 [ 0 => array:4 [ "autoresLista" => "Maria Rita Carvalho Garbi Novaes, Fabiana Valadares, Mariana Campos Reis, Daniella Rodrigues Gonçalves, Marilia da Cunha Menezes" "autores" => array:5 [ 0 => array:4 [ "nombre" => "Maria Rita Carvalho Garbi" "apellidos" => "Novaes" "email" => array:1 [ 0 => "ritanovaes@ig.com.br" ] "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "*" "identificador" => "cor1" ] ] ] 1 => array:2 [ "nombre" => "Fabiana" "apellidos" => "Valadares" ] 2 => array:2 [ "nombre" => "Mariana Campos" "apellidos" => "Reis" ] 3 => array:2 [ "nombre" => "Daniella Rodrigues" "apellidos" => "Gonçalves" ] 4 => array:2 [ "nombre" => "Marilia" "apellidos" => "da Cunha Menezes" ] ] "afiliaciones" => array:1 [ 0 => array:2 [ "entidad" => "Universidade de Brasília, School of Medicine, Institute of Health Science (ESCS), Brasília/DF, Brazil." "identificador" => "aff1" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor1" "etiqueta" => "*" "correspondencia" => "Tel.: 55 61 3254-0925" ] ] ] ] "textoCompleto" => "<span class="elsevierStyleSections"><span id="cesec10" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cestitle20">INTRODUCTION</span><p id="para10" class="elsevierStylePara elsevierViewall">Breast cancer is highly prevalent in women. In 2008, the IARC/OMS estimated that breast cancer was the second biggest incidence of cancer in the world (1.29 million cases). In Brazil, it would be responsible for 49,000 new cases in women from 2010 to 2011 and the mortality rate for this type of cancer remains high, on one side, due to the fact that this disease continues to be diagnosed at advanced stages.<a class="elsevierStyleCrossRefs" href="#bib1">1,2</a></p><p id="para20" class="elsevierStylePara elsevierViewall">Treatment for breast cancer is complex and varies according to the histological diagnosis of the patient, the patient's age, the disease stage and the therapeutic approaches taken.<a class="elsevierStyleCrossRef" href="#bib3">3</a></p><p id="para30" class="elsevierStylePara elsevierViewall">Factors associated with tumor growth and the conventional treatments used to treat cancer often result in malnutrition in breast cancer patients. Side effects caused by conventional treatments, significantly reduced caloric intake and decreased absorption of nutrients can all complicate cancer treatment and reduce the quality of life of cancer patients.<a class="elsevierStyleCrossRef" href="#bib4">4</a></p><p id="para40" class="elsevierStylePara elsevierViewall">Previous studies have sought to identify ways to improve the quality of life and nutritional status of cancer patients using adjuvant therapy with mushrooms.<a class="elsevierStyleCrossRefs" href="#bib4">4–10</a></p><p id="para50" class="elsevierStylePara elsevierViewall">The most recent studies have shown that dietary supplementation with <span class="elsevierStyleItalic">Agaricales</span> mushrooms and other medicinal fungi in breast cancer patients can provide benefits, such as antiproliferative and immunomodulatory effects on tumor cells.<a class="elsevierStyleCrossRefs" href="#bib11">11–15</a></p><p id="para60" class="elsevierStylePara elsevierViewall">The aim of this study is to analyze the effects of mushrooms and other basidiomycetous <span class="elsevierStyleItalic">Agaricales</span> as adjuvant treatments in breast cancer.</p></span><span id="cesec20" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cestitle30">MATERIALS AND METHODS</span><p id="para70" class="elsevierStylePara elsevierViewall">A critical review of articles published in refereed journals between January, 1990 to March, 2011 was performed. Articles were identified in the Medline, Lilacs, Scielo, and Pubmed, Health Science Descriptors (DeCS) and Medical Subject Heading (MeSH) databases by searching for the following terms: in English (<span class="elsevierStyleItalic">Agaricales</span>, <span class="elsevierStyleItalic">Agaricus</span>, medicinal mushroom/fungus, breast cancer, dietary supplementation, edible mushroom effects, lectin), in Portuguese (câncer de mama, cogumelo medicinal), in Spanish (cáncer de mama, suplementación nutricional/dietética, cogumelos, hongos medicinales).</p><p id="para80" class="elsevierStylePara elsevierViewall">Articles identified in the indexing databases mentioned above, including both original articles and reviews of the bioactive effects of edible mushrooms on cancer, were selected for inclusion in this study. Experimental trials in animals evaluating the efficacy of medicinal fungi treatments in breast cancer and randomized clinical trials with <span class="elsevierStyleItalic">Agaricales</span> mushrooms (and other medicinal fungi) in humans with breast cancer were also included.</p></span><span id="cesec30" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cestitle40">RESULTS AND DISCUSSION</span><span id="cesec40" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cestitle50">Bioactive substances found in mushrooms and other <span class="elsevierStyleItalic">Agaricales</span> medicinal fungi</span><p id="para90" class="elsevierStylePara elsevierViewall">The therapeutic effects of medicinal mushrooms are due to the presence of lectin, β-glucan, ergosterol, arginine, and other bioactive substances in mushrooms.<a class="elsevierStyleCrossRefs" href="#bib5">5–9</a> The benefits and possible mechanisms of action of these substances are described in <a class="elsevierStyleCrossRef" href="#tbl1">Table 1</a>.</p><elsevierMultimedia ident="tbl1"></elsevierMultimedia><p id="para100" class="elsevierStylePara elsevierViewall">Lectins have been shown to be therapeutic agents with anticancer properties in animals and in clinical studies. They cause cytotoxicity and apoptosis and inhibition of tumor growth by preferentially binding to cancer cell membranes. Lectins function by sequestering the body's polyamines, thereby inhibiting cancer cell growth. Lectins also alter the production of many interleukins, activate protein kinases, bind to ribosomes, and inhibit protein synthesis. In addition, lectins modify the cell cycle by inducing cell cycle arrest at the G2/M phase, promoting apoptosis, and stimulating non-apoptotic G1-phase accumulation mechanisms. Finally, lectins can also down-regulate telomerase activity and inhibit angiogenesis.<a class="elsevierStyleCrossRefs" href="#bib16">16–20</a></p><p id="para110" class="elsevierStylePara elsevierViewall">β-glucan is a glucose polymer present in medicinal mushrooms. It exhibits immunomodulatory effects as well as tumoricidal and antiproliferative activities in cancer patients through the stimulation of natural killer cells, neutrophils, monocytes, macrophages, and T-cells.<a class="elsevierStyleCrossRefs" href="#bib21">21–28</a></p><p id="para120" class="elsevierStylePara elsevierViewall">Ergosterol (or provitamin D2) is a precursor of ergocalciferol, an important substrate in vitamin D biosynthesis and is found in the lipid fraction of <span class="elsevierStyleItalic">Agaricales</span> extracts. This substance has antitumor, antiproliferation, and antimigratory effects on human cancer cells.<a class="elsevierStyleCrossRefs" href="#bib25">25–27</a> It has also been shown to inhibit angiogenesis. In a study on sarcoma 180 cells, patients treated with ergosterol demonstrated delayed tumor growth with minimal side effects. For example, the decrease in lymphocyte count that is commonly caused by chemotherapy was not observed in these patients. Ergosterol appears to have no direct <span class="elsevierStyleItalic">in vitro</span> cytotoxic effects on tumor cells, although it inhibits tumor-induced neovascularization.<a class="elsevierStyleCrossRef" href="#bib28">28</a></p><p id="para130" class="elsevierStylePara elsevierViewall">Arginine is a semi-essential amino acid used as a dietary supplement in cancer patients. It has been associated with a reduction of tumor growth and metastasis progression, and it is reported to have beneficial effects on the immune system, weight gain, and the time of survival of cancer patients.<a class="elsevierStyleCrossRefs" href="#bib29">29,30</a></p><p id="para140" class="elsevierStylePara elsevierViewall">A complete understanding of the actions of these fungi and their bioactive molecules in the prevention and treatment of cancer will require further investigation. However, research shows that many of these substances exert anticarcinogenic, antiviral, antithrombotic, antibiotic, and anti-inflammatory effects in addition to many other activities that provide health benefits.<a class="elsevierStyleCrossRefs" href="#bib5">5,6,9,31–32</a></p></span><span id="cesec50" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cestitle60">Experimental studies with mushrooms and other <span class="elsevierStyleItalic">Agaricales</span> medicinal fungi</span><p id="para150" class="elsevierStylePara elsevierViewall">Promising results have been reported in animals and <span class="elsevierStyleItalic">in vitro</span> using medicinal mushrooms in the treatment of breast cancer and several other cancers.<a class="elsevierStyleCrossRefs" href="#bib33">33–49</a><a class="elsevierStyleCrossRef" href="#tbl2">Table 2</a> provides a summary of the studies mentioned below.</p><elsevierMultimedia ident="tbl2"></elsevierMultimedia><p id="para160" class="elsevierStylePara elsevierViewall">Takimoto et al.<a class="elsevierStyleCrossRef" href="#bib33">33</a> demonstrated that rats administered <span class="elsevierStyleItalic">Agaricus blazei</span> extract orally exhibited increased cytotoxic T lymphocyte growth, increased levels of interferon-gamma and an increase in NK cells when compared to water-treated controls. This study indicates that mushroom extracts estimulate cytotoxic activity on both, innate and adaptive immunological systems.</p><p id="para170" class="elsevierStylePara elsevierViewall">Immunomodulatory, antitumor, and antiproliferative effects of lectin isolated from various types of <span class="elsevierStyleItalic">Agaricaceae</span> mushrooms have been demonstrated by Zhao et al.<a class="elsevierStyleCrossRef" href="#bib34">34</a> The lectin contained in <span class="elsevierStyleItalic">Agaricus bisporus</span> has been shown to exhibit an antiproliferative effect on breast cancer cells, and the lectin contained in <span class="elsevierStyleItalic">Tricholoma mongolicum</span> has been shown to have an inhibitory effect on mastocytoma cells (P815) <span class="elsevierStyleItalic">in vitro</span>.</p><p id="para180" class="elsevierStylePara elsevierViewall">In an <span class="elsevierStyleItalic">in vivo</span> study, extracts of <span class="elsevierStyleItalic">Coriolus versicolor</span> promoted significant tumor reductions in mice inoculated with mastocytoma tumor cells and mammary tumors.<a class="elsevierStyleCrossRef" href="#bib35">35</a></p><p id="para190" class="elsevierStylePara elsevierViewall">Chen et al.<a class="elsevierStyleCrossRef" href="#bib36">36</a> examined the ability of an <span class="elsevierStyleItalic">Agaricus bisporus</span> extract to inhibit aromatase at the estrogen receptor <span class="elsevierStyleItalic">in vitro</span> in MCF-7 cells and rat ovarian cells and <span class="elsevierStyleItalic">in vivo</span> in rats. The extract inhibited cell proliferation. The linoleic and linolenic acid present in the extract inhibited aromatase activity by altering or mutating the active sites. The <span class="elsevierStyleItalic">in vivo</span> study showed that the extract decreased proliferation and tumor growth without affecting apoptosis in rats.</p><p id="para200" class="elsevierStylePara elsevierViewall">In studies of breast cancer cells (MFC-7), Grube et al.<a class="elsevierStyleCrossRef" href="#bib37">37</a> showed that <span class="elsevierStyleItalic">Agaricus bisporus</span> extract suppresses the activity of aromatase, resulting in a reduction of estrogen production, which is a major contributor to postmenopausal breast cancer in women.</p><p id="para210" class="elsevierStylePara elsevierViewall">In experiments with breast cancer cells (MDA-MB-231), Thyagarajan et al.<a class="elsevierStyleCrossRef" href="#bib38">38</a> showed that <span class="elsevierStyleItalic">Ganoderma lucidum</span> extract inhibits cell proliferation and the formation of new cell colonies through the negative regulation of the expression of c-myc, an oncogene. The combination of <span class="elsevierStyleItalic">G. lucidum</span> extract with green tea extract demonstrated a synergistic effect by suppressing secretion of urokinase plasminogen, which is a breast cancer cell activator, and thereby suppressed the growth and invasion of metastatic breast cancers.</p><p id="para220" class="elsevierStylePara elsevierViewall">In a study of breast cancer cells (MCF7), Petrova et al.<a class="elsevierStyleCrossRef" href="#bib39">39</a> noted that extracts of fungi significantly inhibited the reporter activity of nuclear factor-kappa β (NF-κβ) by interfering negatively in its activation pathway. The study was conducted with 28 fungi extracts, 40% of which were found to inhibit NF-κβ activity.</p><p id="para230" class="elsevierStylePara elsevierViewall">Gu & Leonard<a class="elsevierStyleCrossRef" href="#bib40">40</a> reported the activities of 38 species of edible mushrooms in estrogen receptor-positive (MCF-7) and negative (MDA-MB-231, BT-20) human breast cancer cells. In aqueous extracts from <span class="elsevierStyleItalic">Coprinellus sp., Flammulina velutipes,</span> and <span class="elsevierStyleItalic">Coprinus comatus</span>, anticancer agents were identified that actively inhibited tumor growth.</p><p id="para240" class="elsevierStylePara elsevierViewall">Fang et al.<a class="elsevierStyleCrossRef" href="#bib41">41</a> conducted an <span class="elsevierStyleItalic">in vitro</span> investigation of fractions of ethyl acetate extracts from Shiitake mushrooms <span class="elsevierStyleItalic">(Lentinus edodes)</span> via biological assays of apoptosis and cell cycle analysis in two human breast carcinoma cell lines (MDA-MB-453 and MCF-7). The authors observed antiproliferative activity in all strains. Apoptosis was induced in 50% of the tumor cell lines via the positive regulation of bax, a pro-apoptotic protein. Cell cycle analysis revealed a decrease in the percentage of cells in S phase, an induction of cdk inhibitors and p21 and a suppression of CDK4 and cyclin D1 activities, thus indicating cell cycle arrest.</p><p id="para250" class="elsevierStylePara elsevierViewall">Studies using MCF-7 and MDA-MB-231 cells evaluated the effectiveness of various types of edible mushroom extracts. Jedinak & Sliva,<a class="elsevierStyleCrossRef" href="#bib42">42</a> using flow cytometry, revealed that <span class="elsevierStyleItalic">Pleorotus ostreatus</span> inhibited the proliferation of these cells in breast and colon cancers via p53-dependent and p53-independent mechanisms. This fungus exerted its effect by inducing the expression of the tumor suppressor p53 and the cyclin-dependent kinase inhibitor p21 (CIP1/WAF1), but at the same time inhibited the phosphorylation of retinoblastoma protein (Rb) in MCF-7 and HT-29 cells, breast and colon cells respectively.<a class="elsevierStyleCrossRef" href="#bib42">42</a></p><p id="para260" class="elsevierStylePara elsevierViewall">A study by Jiang et al.<a class="elsevierStyleCrossRef" href="#bib43">43</a> revealed that <span class="elsevierStyleItalic">Ganoderma lucidum</span> inhibits proliferation of MDA-MB-231 breast cancer cells. By inhibiting Akt and NF-kappaβ activity in MDA-MB-231 cells, <span class="elsevierStyleItalic">Ganoderma lucidum</span> reduced their growth.</p><p id="para270" class="elsevierStylePara elsevierViewall">Talorete et al.<a class="elsevierStyleCrossRef" href="#bib44">44</a> isolated breast cancer cells (MCF-7) and exposed them to an aqueous extract of <span class="elsevierStyleItalic">Agaricus blazei</span>. The results indicated that this extract was able to reduce cell proliferation in 26% compared to the control group, by significantly enhancing the expression of an API gene regulatory complex in the human breast cancer cell line MCF7. This, again, highlights the anticarcinogenic potential of mushrooms.</p><p id="para280" class="elsevierStylePara elsevierViewall">In a study of rats inoculated with breast cancer cells, Vetvicka et al.<a class="elsevierStyleCrossRef" href="#bib45">45</a> observed a reduction in cell proliferation after oral supplementation of β-Glucan extracted from medicinal mushrooms. Likewise, a decrease in the proliferation of cancer cells has been reported in studies carried out by Israilides et al.<a class="elsevierStyleCrossRef" href="#bib46">46</a> with breast cancer cells (MCF-7) and by Sliva et al.<a class="elsevierStyleCrossRef" href="#bib47">47</a> using the MDA-MB-231 cell line.</p></span><span id="cesec60" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cestitle70">Clinical studies with breast cancer patients using <span class="elsevierStyleItalic">Agaricales</span> mushrooms and other medicinal fungi</span><p id="para290" class="elsevierStylePara elsevierViewall">Although there are some inconsistencies in the results of clinical studies regarding the use of medicinal mushrooms as an adjuvant therapy in breast cancer treatment, the majority of studies suggest a beneficial effect (<a class="elsevierStyleCrossRef" href="#tbl3">Table 3</a>).</p><elsevierMultimedia ident="tbl3"></elsevierMultimedia><p id="para300" class="elsevierStylePara elsevierViewall">A study in patients with breast cancer who received four daily doses (1.6 g each) of <span class="elsevierStyleItalic">Agaricus sylvaticus</span> revealed that <span class="elsevierStyleItalic">Agaricus sylvaticus</span> supplementation resulted in an increased number of natural killer (NK) cells in 75.7% of the patients. More than half of the patients were receiving chemotherapy or radiotherapy, which typically reduces the numbers of NK cells in the body.<a class="elsevierStyleCrossRefs" href="#bib45">45,11</a></p><p id="para310" class="elsevierStylePara elsevierViewall">In a clinical study of various cancers, including breast cancer (stage IV), Sliva et al.<a class="elsevierStyleCrossRef" href="#bib47">47</a> provided patients with a complex of immunomodulatory components, including <span class="elsevierStyleItalic">Agaricus blazei</span> tea (10 mg/day). After six months of treatment, some patients had increased NK cell activity, as well as increased levels of TNF-α (tumor necrosis factor), erythrocytes, hemoglobin, and glutathione. In contrast, the number of TNF-α receptors was reduced. Diarrhea and occasional nausea were reported, but the quality of life had improved. The combination of immune-active components was effective in increasing NK cell function and other immunological parameters in patients with advanced stages of cancer, thus providing an effective nutritional combination for the treatment of the late stages of cancer.<a class="elsevierStyleCrossRef" href="#bib47">47</a></p><p id="para320" class="elsevierStylePara elsevierViewall">Gennari et al.<a class="elsevierStyleCrossRef" href="#bib48">48</a> reported a case study of a patient with breast cancer and showed that dietary supplementation with <span class="elsevierStyleItalic">Agaricus sylvaticus</span> increased the number of CD56+ NK cells in the blood and caused a total regression of lung metastasis.</p><p id="para330" class="elsevierStylePara elsevierViewall">Dolby<a class="elsevierStyleCrossRef" href="#bib12">12</a> reported that the D-fraction oβ-D-Glucan (extracted from Maitake) and mushroom tablets of <span class="elsevierStyleItalic">Grifola frondosa</span> had a positive effect on the health status of the 15 breast cancer patients included in the study. This study reported an improvement in the clinical parameters and laboratory test results of patients as well as improvements in their hematological parameters, reductions in the amount of vomiting caused by chemotherapy, increased appetite and reduced anorexia, which can be a side effect of conventional treatments.</p><p id="para340" class="elsevierStylePara elsevierViewall">Hong et al.<a class="elsevierStyleCrossRef" href="#bib7">7</a> conducted a study with 362 breast cancer patients between 30 and 65 years of age. The frequency of ingestion of mushrooms was measured through a specific questionnaire. It was found that both the daily intake and the frequency of consumption were inversely related to the risk of breast cancer, especially in postmenopausal women. Similar results were reported by Shin et al.<a class="elsevierStyleCrossRef" href="#bib14">14</a>; however, in the Shin study, the consumption of medicinal mushrooms showed a strong protective effect against breast cancer in premenopausal women as well.</p><p id="para350" class="elsevierStylePara elsevierViewall">Several published experimental clinical studies have reported that medicinal mushrooms exhibit beneficial effects on the health and quality of life in breast cancer patients. The use of supplements as adjunctive therapies for the treatment of breast cancer has shown promising results, such as antiproliferative effects on tumor cells and immunomodulatory activities in the body. However, few articles have examined the effects of supplementation with medicinal mushrooms for the treatment of breast cancer. Therefore, new protocols for the purpose of conducting clinical trials are required to elucidate the possible mechanisms of action and clinical benefits of these fungi with respect to the survival time, clinical progression and quality of life of breast cancer patients.</p></span></span></span>" "textoCompletoSecciones" => array:1 [ "secciones" => array:6 [ 0 => array:2 [ "identificador" => "xpalclavsec1582415" "titulo" => "KEYWORDS" ] 1 => array:2 [ "identificador" => "cesec10" "titulo" => "INTRODUCTION" ] 2 => array:2 [ "identificador" => "cesec20" "titulo" => "MATERIALS AND METHODS" ] 3 => array:3 [ "identificador" => "cesec30" "titulo" => "RESULTS AND DISCUSSION" "secciones" => array:3 [ 0 => array:2 [ "identificador" => "cesec40" "titulo" => "Bioactive substances found in mushrooms and other Agaricales medicinal fungi" ] 1 => array:2 [ "identificador" => "cesec50" "titulo" => "Experimental studies with mushrooms and other Agaricales medicinal fungi" ] 2 => array:2 [ "identificador" => "cesec60" "titulo" => "Clinical studies with breast cancer patients using Agaricales mushrooms and other medicinal fungi" ] ] ] 4 => array:2 [ "identificador" => "xack639320" "titulo" => "ACKNOWLEDGMENTS" ] 5 => array:1 [ "titulo" => "REFERENCES" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "fechaRecibido" => "2011-05-26" "fechaAceptado" => "2011-07-18" "PalabrasClave" => array:1 [ "en" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "KEYWORDS" "identificador" => "xpalclavsec1582415" "palabras" => array:5 [ 0 => "Nutritional supplement" 1 => "<span class="elsevierStyleItalic">Agaricus sylvaticus</span>" 2 => "Medicinal mushroom" 3 => "Adjuvant treatment" 4 => "Basidiomycetes" ] ] ] ] "tieneResumen" => true "resumen" => array:1 [ "en" => array:1 [ "resumen" => "<span id="ceabs10" class="elsevierStyleSection elsevierViewall"><p id="spara40" class="elsevierStyleSimplePara elsevierViewall">Breast cancer is the most prevalent cancer in women. The most frequent therapeutic approaches for the treatment of this disease are chemotherapy, radiotherapy, hormone therapy, and surgery. Conventional pharmacological treatments cause many harmful side effects in patients. To improve the quality of life of breast cancer patients, researchers have sought alternative adjuvant treatment strategies. To assess the effects of fungi and other basidiomycetes <span class="elsevierStyleItalic">Agaricales</span> on the co-adjuvant treatment of breast cancer, we conducted a literary review of the available scientific evidence. We selected articles published in refereed journals from 1990 to 2011 in Medline, Lilacs, CAPES, Scielo, and Pubmed. Articles written in English, Spanish, and Portuguese were reviewed. We used the following descriptors: <span class="elsevierStyleItalic">Agaricales</span>, medicinal mushroom/fungus, breast cancer, dietary supplementation, synonyms, and related terms. The pharmacological effects of nutritional and medicinal mushrooms have been reported in several experimental clinical studies and have shown promising results in the adjuvant treatment of breast cancer. Adjuvant treatment with mushrooms is associated with improvements in the immunological and hematologic parameters of breast cancer, as well as in the quality of life of these patients. Randomized clinical studies are needed to elucidate the possible mechanisms of action and clinical benefits of these fungi with respect to survival time, disease progression, and metastasis in breast cancer.</p></span>" ] ] "NotaPie" => array:1 [ 0 => array:1 [ "nota" => "<p class="elsevierStyleNotepara" id="cenpara10">No potential conflict of interest was reported.</p> <p class="elsevierStyleNotepara" id="cenpara20">Novaes MRCG participated at the heading, analysis and preparation of the manuscript, obtained a scholarship from the Scientific Iniciation Project of the Institute of Health Science - PIC/FEPECS. Valadares F, Reis MC, Gonçalves DR and Menezes MC were responsible for the collection and analysis of data and production of the final scientific work.</p>" ] ] "multimedia" => array:6 [ 0 => array:7 [ "identificador" => "tbl1" "etiqueta" => "Table 1" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "tabla" => array:1 [ "tablatextoimagen" => array:1 [ 0 => array:1 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><tbody title="tbody"><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="top"><elsevierMultimedia ident="202212011438430691"></elsevierMultimedia> \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] ] ] ] "descripcion" => array:1 [ "en" => "<p id="spara10" class="elsevierStyleSimplePara elsevierViewall">Mechanisms of action of various modulating substances present in mushrooms.</p>" ] ] 1 => array:7 [ "identificador" => "tbl2" "etiqueta" => "Table 2" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "tabla" => array:1 [ "tablatextoimagen" => array:1 [ 0 => array:1 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><tbody title="tbody"><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="top"><elsevierMultimedia ident="202212011438430692"></elsevierMultimedia> \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] ] ] ] "descripcion" => array:1 [ "en" => "<p id="spara20" class="elsevierStyleSimplePara elsevierViewall">The effects of <span class="elsevierStyleItalic">Agaricales</span> mushrooms and other medicinal fungi on breast cancer: experimental studies in animals, <span class="elsevierStyleItalic">in vivo</span> and <span class="elsevierStyleItalic">in vitro.</span></p>" ] ] 2 => array:7 [ "identificador" => "tbl3" "etiqueta" => "Table 3" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "tabla" => array:1 [ "tablatextoimagen" => array:1 [ 0 => array:1 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><tbody title="tbody"><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="top"><elsevierMultimedia ident="202212011438430693"></elsevierMultimedia> \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] ] ] ] "descripcion" => array:1 [ "en" => "<p id="spara30" class="elsevierStyleSimplePara elsevierViewall">The results of clinical studies using <span class="elsevierStyleItalic">Agaricales</span> and other medicinal fungi for dietary supplementation and adjuvant treatment in patients with breast cancer.</p>" ] ] 3 => array:5 [ "identificador" => "202212011438430691" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => false "mostrarDisplay" => true "figura" => array:1 [ 0 => array:4 [ "imagen" => "tb1.jpeg" "Alto" => 1128 "Ancho" => 662 "Tamanyo" => 187634 ] ] ] 4 => array:5 [ "identificador" => "202212011438430692" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => false "mostrarDisplay" => true "figura" => array:1 [ 0 => array:4 [ "imagen" => "tb2.jpeg" "Alto" => 550 "Ancho" => 662 "Tamanyo" => 77290 ] ] ] 5 => array:5 [ "identificador" => "202212011438430693" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => false "mostrarDisplay" => true "figura" => array:1 [ 0 => array:4 [ "imagen" => "tb3.jpeg" "Alto" => 288 "Ancho" => 662 "Tamanyo" => 46527 ] ] ] ] "bibliografia" => array:2 [ "titulo" => "REFERENCES" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "cebibsec10" "bibliografiaReferencia" => array:49 [ 0 => array:3 [ "identificador" => "bib1" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:1 [ "referenciaCompleta" => "Brazil. 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