The immunomodulator PSK induces in vitro cytotoxic activity in tumour cell lines via arrest of cell cycle and induction of apoptosis

Background Protein-bound polysaccharide (PSK) is derived from the CM-101 strain of the fungus Coriolus versicolor and has shown anticancer activity in vitro and in in vivo experimental models and human cancers. Several randomized clinical trials have demonstrated that PSK has great potential in adjuvant cancer therapy, with positive results in the adjuvant treatment of gastric, esophageal, colorectal, breast and lung cancers. These studies have suggested the efficacy of PSK as an immunomodulator of biological responses. The precise molecular mechanisms responsible for its biological activity have yet to be fully elucidated.Methods The in vitro cytotoxic anti-tumour activity of PSK has been evaluated in various tumour cell lines derived from leukaemias, melanomas, fibrosarcomas and cervix, lung, pancreas and gastric cancers. Tumour cell proliferation in vitro was measured by BrdU incorporation and viable cell count. Effect of PSK on human peripheral blood lymphocyte (PBL) proliferation in vitro was also analyzed. Studies of cell cycle and apoptosis were performed in PSK-treated cells.Results PSK showed in vitro inhibition of tumour cell proliferation as measured by BrdU incorporation and viable cell count. The inhibition ranged from 22 to 84%. Inhibition mechanisms were identified as cell cycle arrest, with cell accumulation in G0/G1 phase and increase in apoptosis and caspase-3 expression. These results indicate that PSK has a direct cytotoxic activity in vitro, inhibiting tumour cell proliferation. In contrast, PSK shows a synergistic effect with IL-2 that increases PBL proliferation.Conclusion These results indicate that PSK has cytotoxic activity in vitro on tumour cell lines. This new cytotoxic activity of PSK on tumour cells is independent of its previously described immunomodulatory activity on NK cells.AGL was supported by FIS Postdoctoral Research Contract CP03/00111. Studies were partially supported by a grant from Kureha Chemical Industry (Japan)

Effect of viral storm in patients admitted to intensive care units with severe COVID-19 in Spain: a multicentre, prospective, cohort study

Background: The contribution of the virus to the pathogenesis of severe COVID-19 is still unclear. We aimed to evaluate associations between viral RNA load in plasma and host response, complications, and deaths in critically ill patients with COVID-19. Methods: We did a prospective cohort study across 23 hospitals in Spain. We included patients aged 18 years or older with laboratory-confirmed SARS-CoV-2 infection who were admitted to an intensive care unit between March 16, 2020, and Feb 27, 2021. RNA of the SARS-CoV-2 nucleocapsid region 1 (N1) was quantified in plasma samples collected from patients in the first 48 h following admission, using digital PCR. Patients were grouped on the basis of N1 quantity: VIR-N1-Zero ([removed]2747 N1 copies per mL). The primary outcome was all-cause death within 90 days after admission. We evaluated odds ratios (ORs) for the primary outcome between groups using a logistic regression analysis. Findings: 1068 patients met the inclusion criteria, of whom 117 had insufficient plasma samples and 115 had key information missing. 836 patients were included in the analysis, of whom 403 (48%) were in the VIR-N1-Low group, 283 (34%) were in the VIR-N1-Storm group, and 150 (18%) were in the VIR-N1-Zero group. Overall, patients in the VIR-N1-Storm group had the most severe disease: 266 (94%) of 283 patients received invasive mechanical ventilation (IMV), 116 (41%) developed acute kidney injury, 180 (65%) had secondary infections, and 148 (52%) died within 90 days. Patients in the VIR-N1-Zero group had the least severe disease: 81 (54%) of 150 received IMV, 34 (23%) developed acute kidney injury, 47 (32%) had secondary infections, and 26 (17%) died within 90 days (OR for death 0·30, 95% CI 0·16–0·55; p<0·0001, compared with the VIR-N1-Storm group). 106 (26%) of 403 patients in the VIR-N1-Low group died within 90 days (OR for death 0·39, 95% CI 0·26–0·57; p[removed]11 página

The immunomodulator PSK induces cytotoxic activity in tumour cell lines arrest of cell cycle and induction of apoptosis-2

Lture flask and treated with PSK for 96 h, estimating cell viability by means of Trypan blue exclusion. Both agents produced a similar inhibition ofproliferation. NKL cell line was cultured with PSK or neuraminidase treated-PSK and proliferation was determined by BrdU incorporation and absorbance measurement. Both agents induced a similar increase of proliferation. Each column represents the mean of five independent experiments ± SD. *P < 0.001 versus control.<p><b>Copyright information:</b></p><p>Taken from "The immunomodulator PSK induces cytotoxic activity in tumour cell lines arrest of cell cycle and induction of apoptosis"</p><p>http://www.biomedcentral.com/1471-2407/8/78</p><p>BMC Cancer 2008;8():78-78.</p><p>Published online 24 Mar 2008</p><p>PMCID:PMC2291471.</p><p></p

The immunomodulator PSK induces cytotoxic activity in tumour cell lines arrest of cell cycle and induction of apoptosis-5

conjugated monoclonal anti-active-caspase-3 antibody. Data indicate the percentage of cells positive for presence of active-caspase-3. PSK produced increased caspase-3 expression in AGS but not in B9 tumour cell lines. Results are representative of three experiments.<p><b>Copyright information:</b></p><p>Taken from "The immunomodulator PSK induces cytotoxic activity in tumour cell lines arrest of cell cycle and induction of apoptosis"</p><p>http://www.biomedcentral.com/1471-2407/8/78</p><p>BMC Cancer 2008;8():78-78.</p><p>Published online 24 Mar 2008</p><p>PMCID:PMC2291471.</p><p></p

The immunomodulator PSK induces cytotoxic activity in tumour cell lines arrest of cell cycle and induction of apoptosis-3

Corporation and 7-AAD. Data indicate the percentage of cells in each phase of cell cycle. Results are representative of three independent experiments.<p><b>Copyright information:</b></p><p>Taken from "The immunomodulator PSK induces cytotoxic activity in tumour cell lines arrest of cell cycle and induction of apoptosis"</p><p>http://www.biomedcentral.com/1471-2407/8/78</p><p>BMC Cancer 2008;8():78-78.</p><p>Published online 24 Mar 2008</p><p>PMCID:PMC2291471.</p><p></p

The immunomodulator PSK induces cytotoxic activity in tumour cell lines arrest of cell cycle and induction of apoptosis-4

and analyzed by flow cytometry. PSK produced apoptosis in AGS tumour cell line. B9 tumour cell line was also cultured with PSK but apoptosis was not detected in this tumour cell line. All experiments were performed at least three times and gave similar results.<p><b>Copyright information:</b></p><p>Taken from "The immunomodulator PSK induces cytotoxic activity in tumour cell lines arrest of cell cycle and induction of apoptosis"</p><p>http://www.biomedcentral.com/1471-2407/8/78</p><p>BMC Cancer 2008;8():78-78.</p><p>Published online 24 Mar 2008</p><p>PMCID:PMC2291471.</p><p></p

The immunomodulator PSK induces cytotoxic activity in tumour cell lines arrest of cell cycle and induction of apoptosis-0

R 72–96 h. Tumour cells (2.5 to 5 × 10) were plated in quadruplicate in 96-well plates. The proliferation of tumour cells was determined by BrdU incorporation and absorbance measurement. All cell lines analysed showed inhibition of proliferation. Each column represents the mean of five independent experiments ± SD. P < 0.001 versus control.<p><b>Copyright information:</b></p><p>Taken from "The immunomodulator PSK induces cytotoxic activity in tumour cell lines arrest of cell cycle and induction of apoptosis"</p><p>http://www.biomedcentral.com/1471-2407/8/78</p><p>BMC Cancer 2008;8():78-78.</p><p>Published online 24 Mar 2008</p><p>PMCID:PMC2291471.</p><p></p