Effectiveness of qigong and tai chi in the quality of life of patients with cancer: protocol for an umbrella review.

INTRODUCTION: Qigong and tai chi (QTC) have been adopted by many patients with cancer as a complementary treatment with their conventional mainstream cancer management. Findings from current systematic reviews are inconsistent. Some research indicated that either qigong or tai chi interventions could enhance quality of life (QoL), and improve cancer-related symptoms such as fatigue, sleep disturbance and anxiety; while others argued that there was a lack of efficacy of QTC on QoL improvement. This umbrella review will analyse and synthesise the findings from published systematic reviews and meta-analyses regarding the effectiveness of QTC in the QoL of patients with cancer. Twenty-five databases will be searched from their respective inception to December 2021. METHODS AND ANALYSIS: We will conduct a search in 21 English and 4 Chinese databases to identify qualified systematic reviews and meta-analyses. Two reviewers will independently screen all the titles and abstracts, and determine whether the article meets the inclusion criteria. After the identified systematic reviews and/or meta-analyses are confirmed, important information from each article will be extracted to the characteristics table by two reviewers independently. Two reviewers will independently analyse the quality of the selected reviews based on the Assessment of Multiple Systematic Reviews guideline. Findings from the systematic reviews and/or meta-analyses will be summarised and reported. ETHICS AND DISSEMINATION: This review does not require ethics approval as the study is based on the published articles. The results drawn from the present review will be submitted to peer-reviewed journals for publication or presented at conferences. PROSPERO REGISTRATION NUMBER: CRD42021253216.

Biological effects and mechanisms of matrine and other constituents of Sophora flavescens in colorectal cancer.

The plant Sophora flavescens Ait. has been used in the clinical management of colorectal cancer (CRC). Its constituent compounds, notably the alkaloids matrine, oxymatrine, and sophoridine, have received considerable research attention in experimental models of CRC in vivo and in vitro. This review found that extracts of S. flavescens and/or its constituent compounds have been reported to inhibit CRC cell proliferation by inducing cell-cycle arrest at the G1 phase, inducing apoptosis via the intrinsic pathway, interfering in cancer metabolism, inhibiting metastasis and angiogenesis, regulating senescence and telomeres, regulating the tumour microenvironment and down-regulating cancer-related inflammation. In addition, matrine and oxymatrine reversed multi-drug resistance and enhanced the effects of chemotherapies. These anti-cancer effects were associated with regulation of several cellular signalling pathways including: MAPK/ERK, PI3K/AKT/mTOR, p38MAPK, NF-κB, Hippo/LATS2, TGF-ß/Smad, JAK/STAT3, RhoA/ROC, and Wnt/ ß-catenin pathways. These multiple actions in CRC suggest the alkaloids of S. flavescens may be therapeutic candidates for CRC management. Nevertheless, there remains considerable scope for future research into its flavonoid constituents, the effects of combinations of compounds, and the interaction between these compounds and anti-cancer drugs. In addition, more research is needed to investigate likely drug ligand-receptor interactions for each of the bioactive compounds.

Ibrutinib, but not zanubrutinib, induces platelet receptor shedding of GPIb-IX-V complex and integrin αIIbß3 in mice and humans.

The Bruton's tyrosine kinase (Btk) inhibitor ibrutinib has proven to be efficacious in the treatment of B-cell chronic lymphocytic leukemia (B-CLL) and related diseases. However, a major adverse side effect of ibrutinib is bleeding, including major hemorrhages. The bleeding associated with ibrutinib use is thought to be due to a combination of on-target irreversible Btk inhibition, as well as off-target inhibition of other kinases, including EGFR, ITK, JAK3, and Tec kinase. In this study, we investigated the effects of ibrutinib vs zanubrutinib (a more selective Btk inhibitor) on platelet activation, glycoprotein expression, and thrombus formation. Ibrutinib, but not zanubrutinib, induced a time- and dose-dependent shedding of GPIb-IX complex and integrin αIIbß3, but not of GPVI and GPV, from the platelet surface. The shedding of GPIbα and GPIX was blocked by GM6001 and TAPI-2, an ADAM17 inhibitor but not ADAM10 inhibitor. Ibrutinib but not zanubrutinib treatment of human platelets increased ADAM17 activation. Pretreatment of C57BL/6 mice with ibrutinib (10 mg/kg), but not zanubrutinib (10 mg/kg), inhibited ex vivo and in vivo thrombus growth over time. Platelets from ibrutinib-treated patients with CLL showed reduced GPIb-IX complex and integrin αIIbß3 surface expression and reduced ex vivo thrombus formation under arterial flow, which was not observed in zanubrutinib-treated patients. In mice, ibrutinib, but not zanubrutinib, led to increased soluble GPIbα and soluble αIIb levels in plasma. These data demonstrate that ibrutinib induces shedding of GPIbα and GPIX by an ADAM17-dependent mechanism and integrin αIIbß3 by an unknown sheddase, and this process occurs in vivo to regulate thrombus formation.

An innovative anti-cancer Chinese herbal formula exhibited multi-targeted efficacies in metastatic breast cancer mouse model.

BACKGROUND: The incidence and mortality of cancer metastasis is high worldwide. Despite of the chemotherapeutic agents, many cancer patients still take traditional Chinese herbal prescriptions as adjuvant treatments. However, most of these herbal formulae/products lack of evidence-based efficacy. Based on our previous investigations on anti-tumor, anti-angiogenic, anti-metastatic, bone protective and immunomodulating activities of various Chinese herbal medicines, four constituent herbs, namely Andrographis paniculata, Acanthopanax senticosus, Camellia sinensis, and Hedyotis diffusa were eventually selected to form an innovative herbal formula. METHODS: The anti-tumor efficacies of the formula were evaluated in metastatic breast cancer mice model. The bone protective and immunomodulatory effects were also assessed after formula treatment. RESULTS: Our results showed that the breast tumor weight as well as lung and liver metastasis in mice could be reduced after herbal formula treatment for 4 weeks. The breast tumor-induced osteolysis in mice was restored by herbal formula treatment, in which the bone volume in treated mice tibia was comparable to that in the non-tumor bearing normal mice. The IL-12 level was augmented and the survival of mice with metastatic breast tumors was prolonged after treatment. Furthermore, combination of herbal formula with chemotherapeutic agent doxorubicin resulted in better anti-tumor efficacy and increased life span in tumor-bearing mice, when compared with doxorubicin alone treatment. CONCLUSIONS: In summary, our innovative Chinese herbal formula was demonstrated to possess anti-tumor, anti-metastatic and bone-protective activities in metastatic breast tumor-bearing mice. The preclinical data generated in this study would lead to the development of evidence-based supplement as adjuvant therapy for metastatic breast cancer.

Adherence to CONSORT Items in Randomized Controlled Trials of Integrative Medicine for Colorectal Cancer Published in Chinese Journals.

BACKGROUND: The majority of studies of integrative treatment for colorectal cancer (CRC) have been published in Chinese journals. These studies indicate potential benefits, but concerns have been raised over the quality of trials published in Chinese journals. The CONSORT statement provides a guide for study reporting that has been endorsed by more than 400 international journals. Previous studies have used the CONSORT checklist to assess the quality of randomized controlled trials (RCTs). OBJECTIVES: This study focused on RCTs of integrative and traditional medicine for CRC published in Chinese journals and assessed: (1) the overall quality of reporting with a focus on methodological aspects; (2) change over time; and (3) the influence of study funding, level of institution conducting the trial, rank of the journal, and the length of the article. DESIGN: Searches of seven databases identified RCTs. Quality was assessed using CONSORT 2010 with adaptations to facilitate scoring. Additional codes were added for publication year, hospital rank, report length, and status of the journal. Scores of each checklist item, total scores, and scores for eight items associated with RCT methodology were calculated. RESULTS: Eighty-one studies were included in the main analyses. The RCT methodology subgroup scores were significantly higher in studies: with public funding, conducted by authors from university hospitals, published in higher ranked journals, and in longer articles. CONCLUSIONS: Few Chinese journals mention CONSORT in their author guidelines. In these RCTs on CRC better reporting of RCT methodology was associated with ranking of the journal as "core," public funding of the RCT, and first or correspondent author from a university hospital but the quality of reporting had not significantly improved in 15 years. As the volume of scientific information produced in China grows, it is imperative that there is growth in the quality of this information.

Involvement of caspase-4 in IL-1 beta production and pyroptosis in human macrophages during dengue virus infection.

Caspase-4 physically interacts with caspase-1 and is believed to be a proinflammatory caspase that can induce the inflammatory form of programmed cell death (pyroptosis) and the release of mature interleukin (IL)-1ß. However, the function of caspase-4 in dengue virus infection is not yet fully understood. We examined the function of caspase-4 in IL-1ß production and pyroptosis during dengue virus serotype-2 (DENV-2) infection in human macrophages. In this study, DENV-2 infection increased IL-1ß protein level with activated caspase-4 activity. Using primary macrophages, we observed that caspase-4 induces activation of caspase-1 and secretion of IL-1ß in response to DENV-2 infection, without the need for secondary signals to stimulate the assembly of the inflammasome. These findings indicate that the regulation of caspase-1 activity by capsase-4 could represent a unique mechanism. Our data suggest that caspase-4 is upstream of caspase-1 in the pathway that regulates pyroptosis and IL-1ß synthesis in macrophages during DENV-2 infection.

Oxaliplatin-based chemotherapy combined with traditional medicines for neutropenia in colorectal cancer: A meta-analysis of the contributions of specific plants.

This review assessed the effects on chemotherapy induced neutropenia (CIN) of combining oxaliplatin regimens with traditional plant-based medicines (TMs) in the management of colorectal cancer (CRC). 32 RCTs (2224 participants) were included. Meta-analysis showed reduced incidence of grade 3/4 CIN (RR 0.45[0.31, 0.65], I(2)=0%). No studies reported serious adverse events or reduction in tumour response rates associated with concurrent use of oxaliplatin and TM. Due to small sample sizes and risk of bias, these results should be interpreted with caution. Analyses of sub-groups of studies that used similar TM interventions assessed the relative contributions of individual plant-based ingredients to the results. Astragalus, Codonopsis, Atractylodes, Poria and Coix, in various combinations were consistently associated with reduced CIN incidence when administered orally. Experimental studies of these plants have reported reduced myelosuppression and/or enhanced immune response. Further studies of these plants may lead to the development of interventions to supplement conventional CIN treatment.

Distinct expression of interferon-induced protein with tetratricopeptide repeats (IFIT) 1/2/3 and other antiviral genes between subsets of dendritic cells induced by dengue virus 2 infection.

Dengue virus (DENV) infection is an emerging public health hazard threatening inhabitants of the tropics and sub-tropics. Dendritic cells (DCs) are one of the major targets of DENV and the initiators of the innate immune response against the virus. However, current in vitro research on the DENV-DC interaction is hampered by the low availability of ex vivo DCs and donor variation. In the current study, we attempted to develop a novel in vitro DC model using immature DCs derived from the myeloid leukaemia cell line MUTZ-3 (IMDCs) to investigate the DENV-DC interaction. The IMDCs morphologically and phenotypically resembled human immature monocyte-derived dendritic cells (IMMoDCs). However, the permissiveness of IMDCs to DENV2 was lower than that of IMMoDCs. RT-PCR arrays showed that a group of type I interferon (IFN) -inducible genes, especially IFIT1, IFITM1, and IFI27, were significantly up-regulated in IMMoDCs but not in IMDCs after DENV2 infection. Further investigation revealed that IFIT genes were spontaneously expressed at both transcriptional and protein levels in the naive IMDCs but not in the naive IMMoDCs. It is possible that the poor permissiveness of IMDCs to DENV2 was a result of the high basal levels of IFIT proteins. We conclude that the IMDC model, although less permissive to DENV2, is a useful platform for studying the suppression mechanism of DENV2 and we expand the knowledge of cellular factors that modulate DENV2 infection in the human body.

Evaluation of Selected Immunomodulatory Glycoproteins as an Adjunct to Cancer Immunotherapy.

Polysaccharopeptide (PSP), from Coriolus versicolor, has been used widely as an adjuvant to chemotherapy with demonstrated anti-tumor and broad immunomodulating effects. While PSP's mechanism of action still remains unknown, its enhanced immunomodulatory potential with acacia gum is of great interest. Acacia gum, which also contains polysaccharides and glycoproteins, has been demonstrated to be immunopotentiating. To elucidate whether PSP directly activates T-cell-dependent B-cell responses in vivo, we used a well-established hapten carrier system (Nitrophenyl-chicken gamma globulin (NP-CGG)). 6-week C57BL/6 male mice were immunised with 50 µg of NP25-CGG alum precipitate intraperitoneally. Mice were gavaged daily with 50 mg/kg PSP in a vehicle containing acacia gum and sacrificed at days 0, 4, 7, 10, 14 and 21. ELISA was used to measure the total and relative hapten-specific anti-NP IgA, IgM and IgG titre levels compared to the controls. It was found that PSP, combined with acacia gum, significantly increased total IgG titre levels at day 4 (P< 0.05), decreased IgM titre levels at days 4 and 21 (P< 0.05) with no alterations observed in the IgA or IgE titre levels at any of the time points measured. Our results suggest that while PSP combined with acacia gum appears to exert weak immunological effects through specific T-cell dependent B-cell responses, they are likely to be broad and non-specific which supports the current literature on PSP. We report for the first time the application of a well-established hapten-carrier system that can be used to characterise and delineate specific T-cell dependent B-cell responses of potential immunomodulatory glycoprotein-based herbal medicines combinations in vivo.

Application of genetic algorithm for discovery of core effective formulae in TCM clinical data.

Research on core and effective formulae (CEF) does not only summarize traditional Chinese medicine (TCM) treatment experience, it also helps to reveal the underlying knowledge in the formulation of a TCM prescription. In this paper, CEF discovery from tumor clinical data is discussed. The concepts of confidence, support, and effectiveness of the CEF are defined. Genetic algorithm (GA) is applied to find the CEF from a lung cancer dataset with 595 records from 161 patients. The results had 9 CEF with positive fitness values with 15 distinct herbs. The CEF have all had relative high average confidence and support. A herb-herb network was constructed and it shows that all the herbs in CEF are core herbs. The dataset was divided into CEF group and non-CEF group. The effective proportions of former group are significantly greater than those of latter group. A Synergy index (SI) was defined to evaluate the interaction between two herbs. There were 4 pairs of herbs with high SI values to indicate the synergy between the herbs. All the results agreed with the TCM theory, which demonstrates the feasibility of our approach.

Lessons learnt from evidence-based approach of using chinese herbal medicines in liver cancer.

This paper is a systematic review of evidence-based studies of the effectiveness of Chinese herbal medicine (CHM) in the treatment of liver cancer. After a detailed analysis of the literature, five animal studies and four human clinical trials met the criteria for inclusion. Analysis revealed that results of the clinical trials, whilst encouraging, need to be interpreted with caution as problems with study designs may lead to apparent benefits being attributable to various forms of bias. However, as each of the CHM agents used in these studies appeared to be potentially beneficial, further well-designed and controlled randomized clinical trials are warranted. The second part of this review focused on the lessons learned from the relationships between Traditional Chinese Medicine (TCM) theory, TCM Syndrome Differentiation, and modern scientific understanding of mechanisms of action of CHM agents. The understanding of TCM Syndrome Differentiation may allow identification of different patterns of disharmony and may provide important guidance to the prescription of CHM. Furthermore, quality control using both biological and chemical fingerprinting of CHM is important to ensure batch-to-batch consistency to deliver sustained therapeutic benefit. Also, careful assessment of herb-drug interactions is paramount for safety and integrative use of western chemotherapeutic and CHM agents.

PSP activates monocytes in resting human peripheral blood mononuclear cells: immunomodulatory implications for cancer treatment.

Polysaccharopeptide (PSP), from Coriolus versicolor, has been used as an adjuvant to chemotherapy, and has demonstrated anti-tumor and immunomodulating effects. However its mechanism remains unknown. To elucidate how PSP affects immune populations, we compared PSP treatments both with and without prior incubation in phytohaemagglutinin (PHA) - a process commonly used in immune population experimentation. We first standardised a capillary electrophoresis fingerprinting technique for PSP identification and characterisation. We then established the proliferative capability of PSP on various immune populations in peripheral blood mononuclear cells, using flow cytometry, without prior PHA treatment. It was found that PSP significantly increased the number of monocytes (CD14(+)/CD16(-)) compared to controls without PHA. This increase in monocytes was confirmed using another antibody panel of CD14 and MHCII. In contrast, proliferations of T-cells, NK, and B-cells were not significantly changed by PSP. Thus, stimulating monocyte/macrophage function with PSP could be an effective therapeutic intervention in targeting tumors.

The immunomodulatory and anticancer properties of propolis.

Propolis, a waxy substance produced by the honeybee, has been adopted as a form of folk medicine since ancient times. It has a wide spectrum of alleged applications including potential anti-infection and anticancer effects. Many of the therapeutic effects can be attributed to its immunomodulatory functions. The composition of propolis can vary according to the geographic locations from where the bees obtained the ingredients. Two main immunopotent chemicals have been identified as caffeic acid phenethyl ester (CAPE) and artepillin C. Propolis, CAPE, and artepillin C have been shown to exert summative immunosuppressive function on T lymphocyte subsets but paradoxically activate macrophage function. On the other hand, they also have potential antitumor properties by different postulated mechanisms such as suppressing cancer cells proliferation via its anti-inflammatory effects; decreasing the cancer stem cell populations; blocking specific oncogene signaling pathways; exerting antiangiogenic effects; and modulating the tumor microenvironment. The good bioavailability by the oral route and good historical safety profile makes propolis an ideal adjuvant agent for future immunomodulatory or anticancer regimens. However, standardized quality controls and good design clinical trials are essential before either propolis or its active ingredients can be adopted routinely in our future therapeutic armamentarium.

Investigation of the biosynthetic potential of endophytes in traditional Chinese anticancer herbs.

Traditional Chinese medicine encompasses a rich empirical knowledge of the use of plants for the treatment of disease. In addition, the microorganisms associated with medicinal plants are also of interest as the producers of the compounds responsible for the observed plant bioactivity. The present study has pioneered the use of genetic screening to assess the potential of endophytes to synthesize bioactive compounds, as indicated by the presence of non-ribosomal peptide synthetase (NRPS) and polyketide synthase (PKS) genes. The total DNA extracts of 30 traditional Chinese herbs, were screened for functional genes involved in the biosynthesis of bioactive compounds. The four PCR screens were successful in targeting four bacterial PKS, six bacterial NRPS, ten fungal PKS and three fungal NRPS gene fragments. Analysis of the detected endophyte gene fragments afforded consideration of the possible bioactivity of the natural products produced by endophytes in medicinal herbs. This investigation describes a rapid method for the initial screening of medicinal herbs and has highlighted a subset of those plants that host endophytes with biosynthetic potential. These selected plants can be the focus of more comprehensive endophyte isolation and natural product studies.

Culturable endophytes of medicinal plants and the genetic basis for their bioactivity.

The bioactive compounds of medicinal plants are products of the plant itself or of endophytes living inside the plant. Endophytes isolated from eight different anticancer plants collected in Yunnan, China, were characterized by diverse 16S and 18S rRNA gene phylogenies. A functional gene-based molecular screening strategy was used to target nonribosomal peptide synthetase (NRPS) and type I polyketide synthase (PKS) genes in endophytes. Bioinformatic analysis of these biosynthetic pathways facilitated inference of the potential bioactivity of endophyte natural products, suggesting that the isolated endophytes are capable of producing a plethora of secondary metabolites. All of the endophyte culture broth extracts demonstrated antiproliferative effects in at least one test assay, either cytotoxic, antibacterial or antifungal. From the perspective of natural product discovery, this study confirms the potential for endophytes from medicinal plants to produce anticancer, antibacterial and antifungal compounds. In addition, PKS and NRPS gene screening is a valuable method for screening isolates of biosynthetic potential.

Factors influencing the abundance of the side population in a human myeloma cell line.

Side population (SP) refers to a group of cells, which is capable to efflux Hoechst 33342, a DNA-binding dye. SP cells exist both in normal and tumor tissues. Although SP abundance has been used as an indicator for disease prognostic and drug screening in many research projects, few studies have systematically examined the factors influencing SP analysis. In this study we aim to develop a more thorough understanding of the multiple factors involved in SP analysis including Hoechst 33342 staining and cell culture. RPMI-8226, a high SP percentage (SP%) human myeloma cell line was employed here. The results showed that SP% was subject to staining conditions including: viable cell proportion, dye concentration, staining cell density, incubation duration, staining volume, and mix interval. In addition, SP% was highest in day one after passage, while dropped steadily over time. This study shows that both staining conditions and culture duration can significantly affect SP%. In this case, any conclusions based on SP% should be interpreted cautiously. The relation between culture duration and SP% suggests that the incidence of SP cells may be related to cell proliferation and cell cycle phase. Maintaining these technical variables consistently is essential in SP research.

Brazilian green propolis and its constituent, Artepillin C inhibits allogeneic activated human CD4 T cells expansion and activation.

ETHNOPHARMACOLOGICAL RELEVANCE: Propolis has long been used as a popular folk medicine by various ethnic groups due to its wide spectrum of alleged biological and pharmaceutical properties including anti-microbial, anti-cancer and anti-inflammatory functions. All these can be linked to the modulation of immune function. Therefore, it will be relevant for us to find out whether there is any novel compound that can account for such action and the mechanism involved. AIM OF THE STUDY: We investigated the immune modulating effect of Brazilian green propolis (PBrazil) and its constituent Artepillin C (Art-C) by using mixed leukocytes reaction. MATERIALS AND METHODS: The cytotoxic effect of Art-C on non-tumorigenic human liver cell line miHA and non-tumorigenic human kidney cell line HK-2 as well as human peripheral blood mononuclear cells (PBMCs) were measured by XTT cell proliferation assay. The effect of PBrazil and Art-C on T cell proliferation and activation were determined by using carboxyfluorescein succinimidyl ester (CFSE) and by CD25 expression, respectively. Cytokines including tumor necrosis factor-α (TNF-α), interferon-gamma (IFN-γ), interleukins such as IL-2, IL-17 were measured by intracellular cytokine staining and IL-10 was measured by ELISA. The effect of PBrazil and Art-C on regulatory T cells (Treg) induction was determined by the Foxp3 expression. The apoptotic effect of these compounds on CFSE labeled alloreactive T cells was measured by using Annexin V. RESULTS: Using mixed leukocytes reaction we demonstrated for the first time that both Art-C and PBrazil significantly inhibited the alloreactive CD4 T cell proliferation, activation, and suppressed the expressions of IL-2, IFN-γ and IL-17 in these alloreactive CD4 T cells. The inhibitions of Art-C and PBrazil on CD4 T cells were not due to direct cytotoxic effect on PBMC or inducing regulatory T cells differentiation. Both Art-C and PBrazil were found to selectively induce apoptosis in proliferating T cells. The anti-proliferative effect of Art-C and PBrazil were reversible and were also applied to the activated T cells. CONCLUSIONS: In conclusion, our results indicated that Art-C and PBrazil can suppress alloreactive CD4 T cell responses in vitro, suggesting that Art-C could be used as a potential immunosuppressant, either solely or as adjunct agent in treating graft versus host disease.

Supplements for immune enhancement in hematologic malignancies.

This brief review aims to discuss the various cellular immunological aspects and related mechanisms of the use of specific components from traditional herbal medicines. We begin with lessons learned from thalidomide as an effective single drug with multiple mechanisms of action to treat multiple myeloma. Examples of "supplements" or integrative therapy will be drawn from arsenic trioxide, medicinal mushrooms including Coriolus vesicular and Ganoderma lucidum, followed by the discussion of beta-glucans affecting various immunological important cellular subsets. Different classes of compounds may enhance distinct immune cell populations that might contribute to a multi-targeted holistic effects on anti-cancer treatment. Finally, we conclude by highlighting an herbal formulation PHY906 as a potential adjunct to chemotherapy that might become one of the first US Food and Drug Administration (FDA) approved oral herbal medicines for anti-cancer adjunct treatment.

The effects of beta-glucan on human immune and cancer cells.

Non-prescriptional use of medicinal herbs among cancer patients is common around the world. The alleged anti-cancer effects of most herbal extracts are mainly based on studies derived from in vitro or in vivo animal experiments. The current information suggests that these herbal extracts exert their biological effect either through cytotoxic or immunomodulatory mechanisms. One of the active compounds responsible for the immune effects of herbal products is in the form of complex polysaccharides known as beta-glucans. beta-glucans are ubiquitously found in both bacterial or fungal cell walls and have been implicated in the initiation of anti-microbial immune response. Based on in vitro studies, beta-glucans act on several immune receptors including Dectin-1, complement receptor (CR3) and TLR-2/6 and trigger a group of immune cells including macrophages, neutrophils, monocytes, natural killer cells and dendritic cells. As a consequence, both innate and adaptive response can be modulated by beta-glucans and they can also enhance opsonic and non-opsonic phagocytosis. In animal studies, after oral administration, the specific backbone 1-->3 linear beta-glycosidic chain of beta-glucans cannot be digested. Most beta-glucans enter the proximal small intestine and some are captured by the macrophages. They are internalized and fragmented within the cells, then transported by the macrophages to the marrow and endothelial reticular system. The small beta-glucans fragments are eventually released by the macrophages and taken up by other immune cells leading to various immune responses. However, beta-glucans of different sizes and branching patterns may have significantly variable immune potency. Careful selection of appropriate beta-glucans is essential if we wish to investigate the effects of beta-glucans clinically. So far, no good quality clinical trial data is available on assessing the effectiveness of purified beta-glucans among cancer patients. Future effort should direct at performing well-designed clinical trials to verify the actual clinical efficacy of beta-glucans or beta-glucans containing compounds.

High-throughput screening platform for anticancer therapeutic drug cytotoxicity.

There are substances that kill cancer cells, but induce T cell proliferation, like thalidomide. To find more of these, a new anticancer drug screening strategy is vital. In this study we report the development of a differential cytotoxicity screening or evaluation platform using the CellTiter-Glo (Promega, Annandale, NSW, Australia) luminescent cell viability assay (ATP assay) and also the CellTiter 96 AQueous (Promega) one solution cell proliferation assay [3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium, inner salt (MTS) assay]. The results suggested the platform consisting of the combination of the ATP assay be used for quantifying peripheral blood mononuclear cells, while the more economic MTS colorimetric assay is well suited to be used detecting cell viability of cancer cells. In addition, we found paclitaxel (Taxol, MP Biomedicals Australasia Pty Ltd., Seven Hills, NSW, Australia) to be a useful control for this routine screening methodology. Taxol exhibits the desirable in vitro feature of differential cytotoxicity that spares the immunological cells, when used at a concentration that will kill the majority of the cancer cell population.