Radioprotective and anticancer efficacies of Ganoderma Lucidum in a mouse tumor model

2021 ◽  
Vol 07 ◽  
Author(s):  
Yeun-Hwa Gu ◽  
Takenori Yamashita ◽  
Ki-Mun Kang ◽  
Tota Inoue
Keyword(s):  
Antioxidant Activity ◽  
Tumor Growth ◽  
Natural Killer ◽  
Ganoderma Lucidum ◽  
Tumor Model ◽  
Whole Body ◽  
Mouse Tumor ◽  
Cell Numbers ◽  
Icr Mice ◽  
Plasma Antioxidant

Background: Radiation dose is limited by deleterious nontarget effects, such as immunosuppression, necessitating the development of safe radioprotectants. In this study, we examined the radioprotective and anticancer efficacies of the traditional medicinal mushroom Ganoderma lucidum (GL) in a mouse xenograft tumor model. Methods: An aqueous extract was prepared from raw GL and administered by intraperitoneal injection. For the assessment of antitumor efficacy, ICR mice were inoculated with Sarcoma 180 cells and tumor growth (size and weight) compared among control (no treatment), GL alone, radiation alone, and GL plus radiation groups. For the assessment of the protection of the immune system, ICR mice received whole-body irradiation at 2 Gy for 2 weeks or longer with or without intraperitoneal GL administration, and changes in leukocyte, lymphocyte, and monocyte counts were measured. To examine the antioxidant efficacy of GL, ICR mice received whole-body radiation at 2 Gy with or without GL and plasma antioxidant activity measured by the luminol method. Results: Finally, the effects of GL on T helper (CD4-positive) and natural killer (CD8-positive) cell numbers were measured in C57BL mice by flow cytometry. GL administration alone suppressed tumor growth and the tumor-associated increase in lymphocyte and monocyte numbers. In addition, GL enhanced plasma antioxidant activity as well as both helper and natural killer T cell numbers in the presence and absence of irradiation. Conclusion: Collectively, these results demonstrate the antitumor and radioprotective efficacies of GL, which are likely mediated by protection against oxidative stress and preservation of immune cell populations.

Combination of TLR9 agonists EnanDIM with checkpoint inhibitors for cancer immunotherapy.

2017 ◽  
Vol 35 (7_suppl) ◽  
pp. 134-134
Author(s):  
Manuel Schmidt ◽  
Kerstin Kapp ◽  
Detlef Oswald ◽  
Burghardt Wittig ◽  
Barbara Volz
Keyword(s):  
Immune System ◽  
Tumor Growth ◽  
Colon Carcinoma ◽  
Mononuclear Cells ◽  
Checkpoint Inhibitors ◽  
Tumor Model ◽  
Tumor Growth Inhibition ◽  
Mouse Tumor ◽  
New Family ◽  
Ifn Alpha

134 Background: TLR9 agonists have shown anti-tumor effects by modulating the innate and adaptive immune system. Ongoing clinical studies support the use of TLR9 agonists for immunotherapeutic approaches. The new family of TLR9 agonists, EnanDIM, consists of linear single-stranded ODN synthesized using L-deoxyribonucleotides (natural enantiomers of D-deoxyribonucleotides) at their 3’-ends to prevent degradation. Therefore, EnanDIM does not own the off-target effects of PTO-modified CpG-ODN. Methods: EnanDIM with varying nucleotid sequences were compared for IFN-alpha response from human peripheral blood mononuclear cells and those molecules inducing the stronges response were selected. A maximum feasible dose (MFD) approach was employed to evaluate their acute toxicity and immunomodulatory properties. In addition, a combinatory approach with aPD-1 was evaluated in an syngeneic colon carcinoma CT26 mouse tumor model. Results: EnanDIM581 and EnanDIM532 were selected due to their pronounced activation of the IFN-alpha pathway in vitro. Safety assessments throughout and a gross necropsy at the end of the study revealed no signs of toxicity despite extremely high doses (300 - 1700 mg/kg). Dose-dependent increase of IP-10 levels in serum was observed between 6 and 24 hours after injection. In the colon carcinoma CT26 model subcutaneous injection of EnanDIM532 and intraperitoneal injection of aPD-1 had a moderate effect on the tumor growth when used in monotherapy (28.3% and 57.0% tumor growth inhibition, TGI). Notably, a combination of EnanDIM532 and aPD-1 further reduced tumor growth (74.7% TGI) and thus prolonged survival of the mice. Conclusions: In conclusion, EnanDIM, a new family of TLR9 agonists and immune surveillance reactivators (ISR), broadly activates the immune system, shows no toxicity in an MFD study and enhances the anti-tumor effects of the aPD-1 checkpoint inhibitor in a pilot study of a murine colon carcinoma tumor model. These data show the promising potential of EnanDIM not only for monotherapeutic but also combinatory approaches.

Inhibition of tumor growth by mouse ROR1 specific antibody in a syngeneic mouse tumor model

2018 ◽  
Vol 193 ◽  
pp. 35-41 ◽  
Author(s):  
Hadi Hassannia ◽  
Mohammad Mehdi Amiri ◽  
Farhad Jadidi-Niaragh ◽  
Reza Hosseini-Ghatar ◽  
Jalal Khoshnoodi ◽  
...  
Keyword(s):  
Tumor Growth ◽  
Specific Antibody ◽  
Tumor Model ◽  
Mouse Tumor ◽  
Mouse Tumor Model ◽  
Syngeneic Mouse ◽  
Inhibition Of Tumor Growth

scholarly journals A Targeted-Covalent Inhibitor of 17β-HSD1 Blocks Two Estrogen-Biosynthesis Pathways: In Vitro (Metabolism) and In Vivo (Xenograft) Studies in T-47D Breast Cancer Models

Cancers ◽  
2021 ◽  
Vol 13 (8) ◽  
pp. 1841
Author(s):  
Donald Poirier ◽  
Jenny Roy ◽  
René Maltais
Keyword(s):  
Breast Cancer ◽  
Tumor Growth ◽  
Therapeutic Potential ◽  
Tumor Model ◽  
Growth Effect ◽  
Mouse Tumor ◽  
Cancer Models ◽  
Model Cell

17β-Hydroxysteroid dehydrogenase type 1 (17β-HSD1) plays an important role in estrogen-dependent breast tumor growth. In addition to being involved in the production of estradiol (E2), the most potent estrogen in women, 17β-HSD1 is also responsible for the production of 5-androsten-3β,17β-diol (5-diol), a weaker estrogen than E2, but whose importance increases after menopause. 17β-HSD1 is therefore a target of choice for the treatment of estrogen-dependent diseases such as breast cancer and endometriosis. After we developed the first targeted-covalent (irreversible) and non-estrogenic inhibitor of 17β-HSD1, a molecule named PBRM, our goal was to demonstrate its therapeutic potential. Enzymatic assays demonstrated that estrone (E1) and dehydroepiandrosterone (DHEA) were transformed into E2 and 5-diol in T-47D human breast cancer cells, and that PBRM was able to block these transformations. Thereafter, we tested PBRM in a mouse tumor model (cell-derived T-47D xenografts). After treatment of ovariectomized (OVX) mice receiving E1 or DHEA, PBRM given orally was able to reduce the tumor growth at the control (OVX) level without any observed toxic effects. Thanks to its irreversible type of inhibition, PBRM retained its anti-tumor growth effect, even after reducing its frequency of administration to only once a week, a clear advantage over reversible inhibitors.

Antitumor Activity of Polysaccharides Extracted from the Spore Powder of Ganoderma Lucidum (Fr.) Karst

2019 ◽  
Vol 17 (4) ◽  
pp. 394-400
Author(s):  
Wu Jiadi ◽  
Fei Dongliang ◽  
Fu Chenghao ◽  
Jiang Chunying ◽  
Zhao Yan ◽  
...  
Keyword(s):  
Antitumor Activity ◽  
Tumor Growth ◽  
Nk Cells ◽  
Cancer Cells ◽  
Ganoderma Lucidum ◽  
Nk Cell ◽  
Granzyme B ◽  
Cell Numbers ◽  
Low Toxicity ◽  
4T1 Cells

Ganoderma lucidum (Fr.) Karst. has attracted much attention for its antitumor activity and low toxicity. In fact, the spores of G. lucidum may have even higher bioactivity than its fruiting body. However, there is no report on how the polysaccharides from broken spores of G. lucidum may suppress tumor growth. To make up for this gap, this article isolates a type of polysaccharide from the spore powder of G. lucidum and explores its effect on tumor growth in mice bearing 4T1 cells. The results show that the spore powder of G. lucidum could inhibit the tumor growth of 4T1-bearing mice by increasing NK cell numbers in two ways. First, the spore powder of G. lucidum suppresses Tregs to increase the percentage of NK cells, thus killing cancer cells in blood. Second, the spore powder of G. lucidum upregulates the expression of CXCR3, which recruits more NK cells from peripheral blood infiltrating in visceral organs, where NK cells secrete more granzyme B, perforin, and interferon gamma to kill cancer cells. To sum up, our research demonstrates the potential of spore powder of G. lucidum in cancer therapy.

scholarly journals Induction of Therapeutic Protection in an HPV16-Associated Mouse Tumor Model Through Targeting the Human Papillomavirus-16 E5 Protein to Dendritic Cells

2021 ◽  
Vol 12 ◽  
Author(s):  
Oscar Badillo-Godinez ◽  
Adolfo Pedroza-Saavedra ◽  
Veronica Valverde-Garduño ◽  
Victor Bermudez-Morales ◽  
Minerva Maldonado-Gama ◽  
...  
Keyword(s):  
T Cells ◽  
Dendritic Cells ◽  
Tumor Growth ◽  
Tumor Cells ◽  
Specific Antigen ◽  
Tumor Model ◽  
Immune Checkpoint Blockade ◽  
Premalignant Lesions ◽  
Mouse Tumor ◽  
Human Papillomavirus 16

HPV E5 is an oncoprotein mainly expressed in premalignant lesions, which makes it an important target for a vaccine to prevent or cure cervical cancer (CC). In this study, we evaluated whether E5 targeted to DEC-205, present in dendritic cells (DCs), could induce a therapeutic protection against HPV16-induced tumor cells in a mouse model. The HPV-16 E5 (16E5) protein was cross-linked to a monoclonal antibody (mAb) specific to mouse DEC-205 (anti-DEC-205:16E5) or to an isotype control mAb (isotype:16E5). Rotavirus VP6 was cross-linked to the mouse anti-DEC-205 mAb (anti-DEC-205:VP6) as a non-specific antigen control. BALB/c mice were inoculated subcutaneously (s.c.) with the 16E5-expressing BMK-16/myc tumor cells, and 7 and 14 days later the mice were immunized s.c. with the conjugates, free 16E5 or PBS in the presence of adjuvant. Tumor growth was monitored to evaluate protection. A strong protective immune response against the tumor cells was induced when the mice were inoculated with the anti-DEC-205:16E5 conjugate, since 70% of the mice controlled the tumor growth and survived, whereas the remaining 30% developed tumors and died by day 72. In contrast, 100% of the mice in the control groups died by day 30. The anti-DEC-205:16E5 conjugate was found to induce 16E5-specific memory T cells, with a Th1/Th17 profile. Both CD4+ and CD8+ T cells contributed to the observed protection. Finally, treating mice that had developed tumors with an anti-PD-1 mAb, delayed the tumor growth for more than 20 days. These results show that targeting 16E5 to DEC-205, alone or combined with an immune checkpoint blockade, could be a promising protocol for the treatment of the early stages of HPV-associated cancer.

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