INVESTIGATION OF REISHI AS A NATURAL THERAPEUTIC FOR INFLAMMATORY BREAST CANCER

灵芝作为炎性乳腺癌天然疗法的研究

• 批准号: 8357105
• 负责人: Michelle M Martínez
• 金额: $ 5.48万
• 依托单位: UNIVERSIDAD CENTRAL DEL CARIBE
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-07-01 至 2012-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8357105
• 关键词: Affect; Agaricales; Biomedical Research; Breast Cancer Cell; Cancer Cell Growth; Cancer Patient; Cancer cell line; Cell Survival; Characteristics; Data; Detection; Development; Disease; E-Cadherin; Environment; Funding; Gelatinase A; Gene Proteins; Genes; Grant; Human; Imaging Techniques; Immune system; Immunocompromised Host; Inflammatory; Invaded; Investigation; Lymphatic System; Malignant - descriptor; Malignant Neoplasms; Mentors; Molecular; Molecular Target; National Center for Research Resources; Nature; Neoplasm Metastasis; Phenotype; Placebos; Primary Neoplasm; Principal Investigator; Public Health; Reishi mushroom; Research; Research Infrastructure; Resources; Risk; Role; Source; Survivors; Therapeutic; Treatment Efficacy; Tumor Cell Invasion; United States National Institutes of Health; Vascular System; cancer cell; career; cost; dietary supplements; impaired capacity; improved; in vivo; killings; lymph nodes; malignant breast neoplasm; mouse model; novel; protein expression; therapeutic target; tumor; tumor progression

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. The proposed study will investigate the in vivo anti-cancer effects of a dietary supplement containing whole mushroom compounds of Reishi on Inflammatory Breast Cancer (IBC) onset and progression. IBC is the most lethal and least understood form of advanced breast cancer. Its lethality originates from its nature of invading the vascular and lymphatic systems and absence of a typical tumor mass. Reishi compounds have been used in cancer to improve the immune system and kill malignant cancer cells. However, the effect of Reishi extract as a natural targeted therapeutic on IBC has not been investigated. Our preliminary data studying a human IBC cell line shows that whole mushroom Reishi extract inhibits IBC progression by affecting genes that contribute to cancer cell survival, invasion, metastasis, and progression. Reishi extract selectively inhibits IBC cell growth and invasion of the tumor environment. Furthermore, Reishi extract inhibits matrix metalloproteinase 2 and 9 secretion, and E-cadherin protein expression, possibly impairing the capacity of tumor spheroid formation that is characteristic of the IBC phenotype, and a requirement for invasion. Our HYPOTHESIS is that Reishi inhibits IBC onset and progression. Our long-term OBJECTIVES are to determine the therapeutic efficacy of whole mushroom Reishi extract, and investigate the molecular mechanisms by which Reishi affects IBC progression. SPECIFIC AIM 1 will determine the in vivo effects of whole mushroom Reishi extract on IBC onset and progression in an immunocompromised mouse model using novel imaging techniques. SPECIFIC AIM 2 will delineate the molecular targets of whole mushroom Reishi extract lymph nodes and primary tumors at the gene and protein level following treatment with placebo or Reishi extract. SPECIFIC AIM 3 will detail the mentoring and career developmental plans for the PI to achieve a successful independent research career. This proposal is UNIQUE in evaluating a role for a dietary supplement in a locally invasive breast cancer. This research is RELEVANT to public health because it promises to advance the understanding and detection of the therapeutic mechanisms of whole mushroom Reishi dietary supplement for this fatal disease and impact IBC patients, those at risk, and survivors of IBC.

该子项目是利用资源的众多研究子项目之一 由 NIH/NCRR 资助的中心拨款提供。子项目的主要支持 并且子项目的主要研究者可能是由其他来源提供的， 包括其他 NIH 来源。 子项目可能列出的总成本 代表子项目使用的中心基础设施的估计数量， NCRR 赠款不直接向子项目或子项目工作人员提供资金。 拟议的研究将调查含有灵芝全蘑菇化合物的膳食补充剂对炎性乳腺癌（IBC）发病和进展的体内抗癌作用。 IBC 是最致命且最不为人所知的晚期乳腺癌形式。其致命性源于其侵入血管和淋巴系统的性质以及不存在典型肿瘤块的性质。灵芝化合物已用于治疗癌症，以改善免疫系统并杀死恶性癌细胞。然而，灵芝提取物作为天然靶向治疗剂对 IBC 的作用尚未得到研究。我们研究人类 IBC 细胞系的初步数据表明，全蘑菇灵芝提取物通过影响有助于癌细胞存活、侵袭、转移和进展的基因来抑制 IBC 进展。灵芝提取物选择性抑制 IBC 细胞生长和侵袭肿瘤环境。此外，灵芝提取物抑制基质金属蛋白酶2和9的分泌以及E-钙粘蛋白的表达，可能损害肿瘤球体形成的能力，这是IBC表型的特征，也是侵袭的必要条件。我们的假设是灵芝能抑制 IBC 的发生和进展。我们的长期目标是确定全蘑菇灵芝提取物的治疗功效，并研究灵芝影响 IBC 进展的分子机制。具体目标 1 将使用新型成像技术确定全蘑菇灵芝提取物对免疫受损小鼠模型中 IBC 发病和进展的体内影响。 SPECIFIC AIM 2 将在安慰剂或灵芝提取物治疗后在基因和蛋白质水平上描绘整个蘑菇灵芝提取物淋巴结和原发性肿瘤的分子靶标。 SPECIFIC AIM 3 将详细介绍 PI 的指导和职业发展计划，以实现成功的独立研究生涯。该提案在评估膳食补充剂在局部浸润性乳腺癌中的作用方面是独一无二的。这项研究与公共健康相关，因为它有望促进对全蘑菇灵芝膳食补充剂治疗这种致命疾病的治疗机制的理解和检测，并对 IBC 患者、高危人群和 IBC 幸存者产生影响。