INVESTIGATION OF REISHI AS A NATURAL THERAPEUTIC FOR INFLAMMATORY BREAST CANCER

灵芝作为炎症性乳腺癌天然治疗剂的研究拟议的研究将研究含有灵芝全蘑菇化合物的膳食补充剂对炎症性乳腺癌（IBC）发病和进展的体内抗癌作用。IBC是最致命和最不了解的晚期乳腺癌形式。其致死性源于其侵入血管和淋巴系统的性质以及缺乏典型的肿瘤肿块。灵芝化合物已被用于癌症，以改善免疫系统和杀死恶性癌细胞。然而，灵芝提取物作为天然靶向治疗剂对IBC的作用尚未研究。我们研究人类IBC细胞系的初步数据显示，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细胞生长和肿瘤环境的侵袭。此外，灵芝提取物抑制基质金属蛋白酶2和9的分泌，和E-钙粘蛋白的蛋白质表达，可能会损害肿瘤球体形成的能力，这是IBC表型的特征，并为入侵的要求。我们的假设是，灵芝抑制IBC的发病和进展。我们的长期研究是确定灵芝提取物的治疗效果，并研究灵芝影响IBC进展的分子机制。特异性目的1将使用新的成像技术在免疫受损小鼠模型中确定整个蘑菇灵芝提取物对IBC发作和进展的体内作用。特异性目的2将描绘与安慰剂或灵芝提取物治疗后，在基因和蛋白质水平的整个蘑菇灵芝提取物淋巴结和原发性肿瘤的分子靶点。具体目标3将详细说明PI的指导和职业发展计划，以实现成功的独立研究生涯。该建议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特的。这项研究与公共卫生有关，因为它有望促进对这种致命疾病的全蘑菇灵芝膳食补充剂的治疗机制的理解和检测，并影响IBC患者，高危人群和IBC幸存者。

Investigation of Reishi as a Natural Therapeutic for Inflammatory Breast Cancer 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.