Alleviating Effect of Active Hexose Correlated Compound (AHCC) on Chemotherapy-Related Adverse Events in Patients with Unresectable Pancreatic Ductal Adenocarcinoma

Yanagimoto, Hiroaki; Satoi, Sohei; Yamamoto, Tomohisa; Hirooka, Satoshi; Yamaki, So; Kotsuka, Masaya; Ryota, Hironori; Michiura, Taku; Inoue, Kentaro; Matsui, Yoshihiko; Tsuta, Koji; Kon, Masanori

doi:10.1080/01635581.2016.1134597

Cited by 14 publications

(14 citation statements)

References 30 publications

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“…There are many reports on the bioactivity and pharmacological benefits of AHCC in mice and humans. Reported benefits include prevention of the adverse effects of anticancer agents [9,10], immunomodulation [11], anti-influenza effects [12], and protection of hepatocytes [13]. In the present study, we found no changes in plasma biochemical indices, in particular those for hepatotoxicity, in mice allowed to freely consume 3% AHCC over 5 days.…”

Section: Discussioncontrasting

confidence: 52%

DNA microarray analysis of gene expression changes in ICR mouse liver following treatment with active hexose correlated compound

Wakame¹,

Nakata²,

Sato³

et al. 2016

Integr Mol Med

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Active hexose correlated compound (AHCC) is a mixture of glucan-rich polysaccharides isolated from the culture extract of shiitake mushroom mycelium. Multiple bioactivities, including immune regulation, have been reported in both basic and clinical studies. This compound has also been used as an adjunct treatment for cancer, but no study has examined whether AHCC can alter the metabolism of therapeutic agents, such as anticancer drugs, in the liver by altering the expression of drug-metabolizing enzymes. Here, we assessed AHCC-induced changes in the expression of genes encoding drug-metabolizing enzymes using a DNA microarray.A 3% AHCC solution was provided ad libitum for 5 days to ICR mice, followed by liver excision, total RNA extraction, and DNA microarray analyses using the Genopal® Metabolic chip (195 genes) and Oxidative stress chip (219 genes). The Metabolic chip identified eight differentially expressed genes (DEGs), defined by a minimum 2.0-fold change in expression from that in control mice. Of these DEGs, two involved in drug metabolism exhibited modest upregulation (CYP3A11, signal intensity ratio [SIR] = 1.15 and CYP7A1, SIR = 1.02). In addition, the Oxidative stress chip identified 23 DEGs, of which five (BCL10, BCL6, ICAM1, MAP3K5, and CASP9) showed very strong suppression (SIR < -10).Oral administration of AHCC to healthy mice altered the expression of multiple genes in the liver, including slight upregulation of drug-metabolizing enzymes and marked suppression of genes involved in tumor necrosis factor signaling and apoptosis. Thus, AHCC may protect liver function against the adverse effects of anticancer agents, such as inflammation, while having little effect on drug metabolism.

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Section: Discussioncontrasting

confidence: 52%

DNA microarray analysis of gene expression changes in ICR mouse liver following treatment with active hexose correlated compound

Wakame¹,

Nakata²,

Sato³

et al. 2016

Integr Mol Med

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“…AHCC likely will not be curative for AML by itself, but still might provide powerful antitumor effects in combination with one or more of these therapies. The potential protective and / or antitumor effects of AHCC in combination with chemotherapeutic agents has been shown to have positive effects within the context of solid tumors including pancreatic, ovarian, lung, colorectal and breast cancer [45–47]. Our results suggest that it may be particularly effective for AML, as it appears to directly induce blast-cell apoptosis without harming later-lineage monocytes.…”

Section: Discussionmentioning

confidence: 70%

“…Perhaps as importantly, AHCC has been shown to reduce the adverse effects seen with chemotherapeutic agents [44–47]. Current AML therapies largely consist of intensive chemotherapy and allogeneic hematopoietic stem cell transplantation, but outcomes in elderly patients are especially poor due to their inability to receive intensive chemotherapy [48].…”

Section: Discussionmentioning

confidence: 99%

Active hexose-correlated compound enhances extrinsic-pathway-mediated apoptosis of Acute Myeloid Leukemic cells

et al. 2017

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Active Hexose Correlated Compound (AHCC) has been shown to have many immunostimulatory and anti-cancer activities in mice and in humans. As a natural product, AHCC has potential to create safer adjuvant therapies in cancer patients. Acute Myeloid Leukemia (AML) is the least curable and second-most common leukemia in adults. AML is especially terminal to those over 60 years old, where median survival is only 5 to 10 months, due to inability to receive intensive chemotherapy. Hence, the purpose of this study was to investigate the effects of AHCC on AML cells both in vitro and in vivo. Results showed that AHCC induced Caspase-3-dependent apoptosis in AML cell lines as well as in primary AML leukopheresis samples. Additionally, AHCC induced Caspase-8 cleavage as well as Fas and TRAIL upregulation, suggesting involvement of the extrinsic apoptotic pathway. In contrast, monocytes from healthy donors showed suppressed Caspase-3 cleavage and lower cell death. When tested in a murine engraftment model of AML, AHCC led to significantly increased survival time and decreased blast counts. These results uncover a mechanism by which AHCC leads to AML-cell specific death, and also lend support for the further investigation of AHCC as a potential adjuvant for the treatment of AML.

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“…We previously reported in a retrospective study that AHCC intake improved the prognosis of postoperative hepatocellular carcinoma (HCC) patients [ 26 ]. Additionally, we indicated that AHCC intake effectively decreased the rate of adverse events and maintained the QOL of patients with unresectable PDAC during chemotherapy in a retrospective study [ 27 ]. AHCC has fewer adverse effect s[ 24 ] and can be considered safe in combination with chemotherapy on the basis of the latest evidence in the treatment of PDAC.…”

Section: Introductionmentioning

confidence: 99%

Efficacy of active hexose correlated compound on survival of patients with resectable/borderline resectable pancreatic cancer: a study protocol for a double-blind randomized phase II study

Hashimoto

Satoi

Ishikawa

et al. 2022

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Background The prognosis of pancreatic ductal adenocarcinoma remains very poor. One possible reason for the short survival of patients with this disease is malnutrition, which can be present at the initial diagnosis, and continue after pancreatectomy. Then, it is important to improve nutritional status and to decrease adverse events during neoadjuvant and adjuvant chemotherapy. Active hexose correlated compound (AHCC) is a standardized extract of cultured Lentinula edodes mycelia, and is considered a potent biological response modifier in the treatment of cancer. To evaluate the survival impact of AHCC on the patients with pancreatic ductal adenocarcinoma, we plan to perform this trial. Methods This is a prospective multicenter phase II trial in patients with resectable/borderline resectable pancreatic ductal adenocarcinoma to investigate the efficacy of AHCC regarding survival. Patients will begin taking AHCC or placebo on the first day of neoadjuvant therapy. AHCC or placebo will be continued until 2 years after surgery. The primary endpoint will be 2-year disease-free survival. The secondary endpoints are the completion rate, dose intensity, and adverse event profile of preoperative chemotherapy; response rate to preoperative chemotherapy; rate of decrease in tumor marker (carbohydrate antigen 19-9, carcinoembryonic antigen) concentrations during preoperative chemotherapy; entry rate, completion rate, dose intensity, and adverse event profile of adjuvant chemotherapy; safety of the protocol therapy (adverse effect of AHCC); 2-year overall survival rate; and nutrition score before and after preoperative chemotherapy, and before and after adjuvant chemotherapy. We will enroll 230 patients, and the study involves eight leading Japanese institutions that are all high-volume centers in pancreatic surgery. Discussion AHCC is expected to function as a supportive food in patients with pancreatic ductal adenocarcinoma, to reduce the proportion of severe adverse events related to neoadjuvant chemotherapy, and to increase the completion proportion of multimodal treatments, resulting in improved survival. Trial registration The trial protocol has been registered in the protocol registration system at the Japan Registry of Clinical Trials (Trial ID: jRCTs051200029). At the time of the submission of this paper (October 2020), the protocol version is 2.0. The completion date is estimated to be November 2024.

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Alleviating Effect of Active Hexose Correlated Compound (AHCC) on Chemotherapy-Related Adverse Events in Patients with Unresectable Pancreatic Ductal Adenocarcinoma

Cited by 14 publications

References 30 publications

DNA microarray analysis of gene expression changes in ICR mouse liver following treatment with active hexose correlated compound

DNA microarray analysis of gene expression changes in ICR mouse liver following treatment with active hexose correlated compound

Active hexose-correlated compound enhances extrinsic-pathway-mediated apoptosis of Acute Myeloid Leukemic cells

Efficacy of active hexose correlated compound on survival of patients with resectable/borderline resectable pancreatic cancer: a study protocol for a double-blind randomized phase II study

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