Modulation of carcinogenesis with selected GRAS nutraceuticals via Keap1-Nrf2 signaling pathway.

Keap1-Nrf2 is a fundamental signaling cascade known to promote or prevent carcinogenesis. Extensive studies identify the key target of modulatory aspects of Keap1-Nrf2 signaling against cancer. Nutraceuticals are those dietary agents with many health benefits that have immense potential for cancer chemoprevention. The nutritional supplements known as nutraceuticals are found to be one of the most promising chemoprevention agents. Upon investigating the dual nature of Nrf2, it became clear that, in addition to shielding normal cells from numerous stresses, Nrf2 may also promote the growth of tumors. In the present review, we performed a systematic analysis of the role of 12 different nutraceuticals like curcumin, sulforaphane, resveratrol, polyunsaturated fatty acids (PUFA) from fish oil, lycopene, soybean, kaempferol, allicin, thymoquinone, quercetin, gingerol, and piperine in modulating the Nrf2/Keap1 signaling mechanism. Among these, 12 Generally Recognized As Safe (GRAS) certified nutraceuticals, sulforaphane is the most extensively studied compound in modulating Keap1-Nrf signaling. Even though there is much evidence at preclinical levels, further high-quality research is still required to validate the potential role of these nutraceuticals in Keap1-Nrf2 modulation.

Decoding Immune Signature to Detect the Risk for Early-Stage HCC Recurrence.

Hepatocellular carcinoma (HCC) is often recognized as an inflammation-linked cancer, which possesses an immunosuppressive tumor microenvironment. Curative treatments such as surgical resection, liver transplantation, and percutaneous ablation are mainly applicable in the early stage and demonstrate significant improvement of survival rate in most patients. However, 70-80% of patients report HCC recurrence within 5 years of curative treatment, representing an important clinical issue. However, there is no effective recurrence marker after surgical and locoregional therapies, thus, tumor size, number, and histological features such as cancer cell differentiation are often considered as risk factors for HCC recurrence. Host immunity plays a critical role in regulating carcinogenesis, and the immune microenvironment characterized by its composition, functional status, and density undergoes significant alterations in each stage of cancer progression. Recent studies reported that analysis of immune contexture could yield valuable information regarding the treatment response, prognosis and recurrence. This review emphasizes the prognostic value of tumors associated with immune factors in HCC recurrence after curative treatment. In particular, we review the immune landscape and immunological factors contributing to early-stage HCC recurrence, and discuss the immunotherapeutic interventions to prevent tumor recurrence following curative treatments.