Higher organisms are all born with general immunity as well as with, increasingly, more specific immune systems. All immune mechanisms function with the intent of aiding the body in defense against infection. Internal and external factors alike have varying effects on the immune system, and the immune response is tailored specifically to each one. Accompanying the components of the human innate and adaptive immune systems are the other intermingling systems of the human body. Increasing understanding of the body's immune interactions with other systems has opened new avenues of study, including that of the microbiome. The microbiome has become a highly active area of research over the last 10 to 20 years since the NIH began funding the Human Microbiome Project (HMP), which was established in 2007. Several publications have focused on the characterization, functions, and complex interplay of the microbiome as it relates to the rest of the body. A dysfunction between the microbiome and the host has been linked to various diseases including cancers, metabolic deficiencies, autoimmune disorders, and infectious diseases. Further understanding of the microbiome and its interaction with the host in relation to diseases is needed in order to understand the implications of microbiome dysfunction and the possible use of microbiota in the prevention of disease. In this review, we have summarized information on the immune system, the microbiome, the microbiome's interplay with other systems, and the association of the immune system and the microbiome in diseases such as diabetes and colorectal cancer.

Akt, also known as protein kinase B (PKB), belongs to the AGC family of protein kinases. It acts downstream of the phosphatidylinositol 3-kinase (PI3K) and regulates diverse cellular processes, including cell proliferation, cell survival, metabolism, tumor growth and metastasis. The PI3K/Akt signaling pathway is frequently deregulated in breast cancer and plays an important role in the development and progression of breast cancer. There are three closely related members in the Akt family, namely Akt1(PKBα), Akt2(PKBβ) and Akt3(PKBγ). Although Akt isoforms share similar structures, they exhibit redundant, distinct as well as opposite functions. While the Akt signaling pathway is an important target for cancer therapy, an understanding of the isoform-specific function of Akt is critical to effectively target this pathway. However, our perception regarding how Akt isoforms contribute to the genesis and progression of breast cancer changes as we gain new knowledge. The purpose of this review article is to analyze current literatures on distinct functions of Akt isoforms in breast cancer.

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Background and Purpose: Copper is a crucial structural component for many significant enzymes, as well as a key catalytic co-factor in redox processes. The flexible Cu(I/II) redox behavior facilitates the formation of copper complexes that are more potent and less toxic. The anticancer activity of several agents can be enhanced by forming copper complexes. The purpose of this study is to evaluate the anti-proliferative effects of two copper (II) complexes, copper-tolfenamic acid (Cu-TA) and copper thiosemicarbazone (Cu-acetylethTSC or CuTSC) against medulloblastoma (MB). MB is a cancer of the cerebellum which is associated with frequent relapse and drug resistance with the current treatments. It necessitates the development of alternative strategies. The anti-cancer activity of Cu-TA was evaluated in laboratory testing in some cancer models, but it has not been studied in MB. CuTSC against colorectal cancer, leukemia and breast cancer has been studied but it has not in MB. Methods: TA and TSC were complexed with Cu and Cu-TA and CuTSC complexes were characterized through colorimetric/mass spectrometric analyses. Cancer cells and cardiomyocytes were cultured using standard protocols and cell viability was measured using Cell Titer-Glo kit (Promega). Protein expression was determined by Western blot analysis. Experiments/Results: CuTA and CuTSC complexes showed proper characterization and stability during the testing period. Cardiomyocytes (H9C2) and human cancer cell lines representing breast, Ewing sarcoma and MB were screened for anti-proliferative activity of these two Cu complexes. While, cell viability was inhibited in all cancer cell lines, MB cell lines (DAOY and D283) showed higher efficacy while H9C2 cell viability was not affected. To understand the underlying mechanism of action, the effect of Cu-TA was assessed on the expression of c-PARP, Specificity protein 1 (Sp1) and an antiapoptotic protein, survivin. Western blot results revealed a clear decrease in the expression of both Sp1 and survivin and upregulation of c-PARP. Discussion/Conclusion: Both Cu-TA and CuTSC treatments result in a dose-time dependent anti-proliferative activity against cancer cells but not affecting non-malignant cardiomyocyte cells. Cu-TA can inhibit Sp1 and survivin and increase PARP cleavage suggesting the effect on Sp1-regulated oncogenes and an induction of apoptotic pathways. The studies to establish crossing of Blood Brain Barrier and further understand the underling mechanisms of these two Cu complexes in single and combination treatment alongside chemotherapeutic agents are currently under investigation. Citation Format: Hope Korshie Fiadjoe, Christoffer Lambring, Umesh T. Sankpal, Duaa Alajroush, Alvin A. Holder, Riyaz Basha. Anti-proliferative effect of two copper complexes against medulloblastoma cells [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 6255.