epiglucan and Stomach-Neoplasms

Lentinan is a beta(1-3) glucan clarified to have a life prolonging effect in non-operable, recurrent gastric cancer patients in combination with chemotherapy. The long lasting issue remaining to be resolved has been the ineffectiveness of Lentinan when administered per-orally. Beta(1-3) glucans possess the particulate size around 100-200 microm in aqueous solution which dampered the absorption through abdominal mucosa. Subsequently the particulate size of Lentinan impaired the immunostimulating potency, to induce reductive form of antigen presenting cells, macrophages and dendritic cells relevant for the polarization of Th1/Th2 balance to Th1. The situation is also the case for the clinical benefit of lentinan to reduce the side effect of chemotherapeutic agents such as TS-1, Gemzar, CDDP, known to be a critical dose limiting factor of these agents and to improve quality of life of the patients. Using the modern nano-technology procedures, Mitherapist, containing 15 mg/dl Lentinan, with a particulate size of 0.2 microm able to pass through mucosal barrier was provided. It was found in randomized double blind clinical testing that Mitherapist is effective against allergy by reducing an antigen specific IgE level through polarization to Th1 biased immune response even by per-oral administration. Per oral administration also exhibited the reduced side effect of chemotherapeutic agents such as TS-1, Gemzar, CDDP and greatly improved quality of life of the cancer patients. The role of hypoxia in local neoplastic tissues will be also discussed.

Topics: Adjuvants, Immunologic; Administration, Oral; Antineoplastic Agents; beta-Glucans; Drug Combinations; Humans; Immunotherapy; Lentinan; Neoplasms; Oxonic Acid; Pyridines; Randomized Controlled Trials as Topic; Stomach Neoplasms; Tegafur

Invasive fungal infection (IFI) related to surgery in elderly patients is often associated with high morbidity and mortality. The aim of the present study was to determine 1,3-β-D-glucan (βDG) levels after gastric cancer surgery in elderly patients and to prospectively evaluate the efficacy of pre-emptive antifungal therapy using βDG as an aid for the early diagnosis of IFI.. In all, 81 patients aged ≥70 years who had undergone gastric cancer surgery between 2009 and 2011 were prospectively enrolled in the study. Patients with plasma βDG levels >11 pg/mL (the cut-off value) were randomly assigned to either receive antifungal treatment or not (n=13 in each group). Postoperative outcomes were assessed using various clinical parameters.. After gastric cancer surgery, plasma βDG levels were ≥11 pg/mL in 26 of 81 elderly patients (32.1%). Of the βDG-positive patients, significantly more had stages III and IV rather than stages I and II disease (44.1% vs 23.4%, respectively; P=0.049). Fever on postoperative day 8 was significantly reduced in the pre-emptive antifungal-treated group than in the control group (36.8°C vs 37.2°C, respectively; P=0.045). However, there were no significant differences in mortality, morbidity, βDG levels, white blood cell count, and C-reactive protein levels between the two groups.. Pre-emptive antifungal treatment based on βDG after gastric surgery in elderly patients may help reduce the incidence of postoperative fever and suppress IFI. However, this needs to be confirmed in a larger prospective randomized, controlled trial.

Topics: Aged; Aged, 80 and over; Antifungal Agents; beta-Glucans; Biomarkers; Early Diagnosis; Female; Gastrectomy; Humans; Male; Mycoses; Neoplasm Staging; Perioperative Care; Postoperative Complications; Prospective Studies; Proteoglycans; Stomach Neoplasms; Treatment Outcome

Based on cancer-related deaths, stomach cancer is ranked fifth, and first among Hispanics. Lack of technologies for early diagnosis and unavailability of target-specific therapeutics are largely the causes of the poor therapeutic outcomes from existing chemotherapeutics. Currently available therapeutic modalities are invasive and require systemic delivery, although the cancer is localized in the stomach at its early stage. Therefore, we hypothesize that an oral local delivery approach can extend the retention duration of the therapeutics modalities within the stomach and thereby enhance therapeutic efficacy. To accomplish this, we have developed a ß-glucan (BG)-based oral delivery vehicle that can adhere to the mucus lining of the stomach for an extended period while controlling the release of Bcl2 siRNA and 5-fluorouracil (5FU) payload for over 6 h. We found that Bcl2 siRNA selectively knocked down the Bcl2 gene in a C57BL/6 stomach cancer mouse model followed by upregulation of apoptosis and remission of cancer. BG was found to be very effective in maintaining the stability of siRNA for at least 6 h, when submerged in simulated gastric juice tested in vitro. To investigate the potential therapeutic effects in vivo, we used a stomach cancer mouse model, where C57BL/6 mice were treated with 5FU, BG/5FU, siRNA, BG/siRNA, and BG/5FU/siRNA. Higher inhibition of Bcl2 and therapeutic efficacy were observed in mice treated with BG/5FU/siRNA confirmed with Western blotting and a TUNEL assay. Significant reduction in the tumor region was observed with histology (H&E) and immunohistochemistry (Ki67, TUNEL, and Bcl2) analyses. Overall, the oral formulation shows improved efficacy with nonsignificant side effects compared to the conventional treatment tested in the gastric cancer mouse model.

Topics: Animals; beta-Glucans; Fluorouracil; Mice; Mice, Inbred C57BL; RNA, Small Interfering; Stomach Neoplasms

Cachexia, a negative prognostic factor, worsens a patient's quality of life. We established 2 novel cachexia models with the human stomach cancer cell line MKN-45, which was subcloned to produce potent cachexia-inducing cells by repeating the xenografts in immune-deficient mice. After subsequent xenografts, we isolated potent cachexia-inducing cells (MKN45cl85 and 85As2mLuc). Xenografts of MKN45cl85 cells in mice led to substantial weight loss and reduced adipose tissue and musculature volumes, whereas xenografts of 85As2mLuc cells resulted in highly metastatic and cachectic mice. Surgical removal of tumor tissues helped the mice regain body-weight in both mouse models. In vitro studies using these cells showed that isoflavones reduced their proliferation, implying that the isoflavones possess antiproliferative effects of these cancer cell lines. Isoflavone treatment on the models induced tumor cytostasis, attenuation of cachexia, and prolonged survival whereas discontinuation of the treatment resulted in progressive tumor growth and weight loss. The inhibitory effects of tumor growth and weight loss by isoflavones were graded as soy isoflavone aglycone AglyMax > daidzein > genistein. These results demonstrated that the 2 novel cachectic mouse models appear useful for analyzing the mechanism of cancer cachexia and monitoring the efficacy of anticachectic agents.

Topics: Animals; beta-Glucans; Cachexia; Cell Line, Tumor; Cell Proliferation; Disease Models, Animal; Female; Genistein; Humans; Isoflavones; Mice; Mice, Inbred BALB C; Neoplasms, Experimental; Stomach Neoplasms; Xenograft Model Antitumor Assays

β-(1,3)-D-Glucan with β-(1,6) branches has been reported to have various pharmacological activities, such as anti-tumour and anti-infection activities, which result from its immunomodulating effects. Gastric lesions result from an imbalance between aggressive and defensive factors. In the present study, we examined the effect of β-(1,3)-D-glucan with β-(1,6) branches isolated from Aureobasidium pullulans on the gastric ulcerogenic response in mice. Oral administration of β-glucan ameliorated gastric lesions induced by ethanol (EtOH) or HCl. This administration of β-glucan also suppressed EtOH-induced inflammatory responses, such as infiltration of neutrophils and expression of pro-inflammatory cytokines, chemokines and cell adhesion molecules (CAM) at the gastric mucosa. Of the various defensive factors, the levels of heat shock protein (HSP) 70 and mucin but not PGE(2) were increased by the administration of β-glucan. β-Glucan-dependent induction of the expression of HSP70 and mucin proteins and suppression of the expression of pro-inflammatory cytokines, chemokines and CAM were also observed in cultured cells in vitro. The results of the present study suggest that β-glucan protects the gastric mucosa from the formation of irritant-induced lesions by increasing the levels of defensive factors, such as HSP70 and mucin.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Carcinoma; Cell Adhesion Molecules; Cells, Cultured; Cytokines; Gastric Mucins; Gastric Mucosa; Gene Expression Regulation; Glucans; HSP70 Heat-Shock Proteins; Humans; Inflammation Mediators; Irritants; Macrophages, Peritoneal; Male; Mice; Mice, Inbred ICR; Neutrophil Infiltration; Protective Agents; RNA, Messenger; Stomach Neoplasms; Stomach Ulcer; Tumor Cells, Cultured