Expression of multidrug resistance-associated protein1,P-glycoprotein, and thymidylate synthase in gastric cancer patients treated with 5-fluorouracil and doxorubicin-based adjuvant chemotherapy after curative resection.
Both 5-fluorouracil and doxorubicin are commonly used agents in chemotherapy of gastric cancer in adjuvant setting as well as metastatic disease. In a variety of malignancies, high expression of multidrug resistance-associated protein1 and P-glycoprotein has been associated with resistance to doxorubicin, whereas 5-fluorouracil resistance has correlated with the level of thymidylate synthase expression. We evaluated the expression of multidrug resistance-associated protein1, P-glycoprotein, and thymidylate synthase using immunohistochemistry in 103 locally advanced gastric cancer patients (stage IB-IV) who underwent 5-fluorouracil and doxorubicin-based adjuvant chemotherapy after curative resection and investigated the association between their expression and clinicopathologic characteristics including prognosis of the patients. While high expression (> or =5% of tumour cells positive) of multidrug resistance-associated protein1 and P-glycoprotein was observed in 70 patients (68%) and 42 patients (41%), respectively, 65 patients (63%) had primary tumours with high expression (> or =25% of tumour cells positive) of thymidylate synthase. There was a significant association between multidrug resistance-associated protein1 and P-glycoprotein expression (P<0.0001) as well as P-glycoprotein and thymidylate synthase expression (P<0.0001). High multidrug resistance-associated protein1 and P-glycoprotein expressions were associated with well and moderately differentiated histology (P<0.0001 and P=0.03, respectively) and intestinal type (P<0.0001 and P=0.009, respectively). High multidrug resistance-associated protein1 expression correlated with lymph node metastasis (P=0.037), advanced stage (P=0.015), and older age (P=0.021). Five-year disease-free survival and overall survival of total patients were 55.2% and 56.2%, respectively, with a median follow-up of 68 months. There were no significant differences in disease-free survival and overall survival according to the expression of multidrug resistance-associated protein1 (P=0.902 and P=0.975, respectively), P-glycoprotein (P=0.987 and P=0.955, respectively), and thymidylate synthase (P=0.604 and P=0.802, respectively). Concurrent high expression of these proteins (high multidrug resistance-associated protein1/P-glycoprotein, high multidrug resistance-associated protein1/thymidylate synthase, high P-glycoprotein/thymidylate synthase) did not correlate with disease-free survival or overall survival. Even high expression of all three proteins was not associated with poor disease-free survival (P=0.919) and overall survival (P=0.852). In conclusion, high expression of multidrug resistance-associated protein1, P-glycoprotein, and thymidylate synthase did not predict poor prognosis of gastric cancer patients treated with 5-fluorouracil and doxorubicin-based adjuvant chemotherapy. A larger study including patients treated with surgical resection alone would be necessary. (+info)
Suppressive effect of polysaccharides from the edible and medicinal mushrooms, Lentinus edodes and Agaricus blazei, on the expression of cytochrome P450s in mice.
To investigate the effects of lentinan from Lentinas edodes and polysaccharides from Agaricus blazei (ABPS) on the expression of cytochrome P450s (CYPs), lentinan (10 mg/kg/day) or ABPS (200 mg/kg/day) was administered to female BALB/c mice four times every other day by intraperitoneal injection. Lentinan and ABPS suppressed both the constitutive and 3-methylcholanthrene-induced CYP1A expression and ethoxyresorufin-O-deethylation activity in the liver. (+info)
beta(1 leads to 3) Glucan-mediated augmentation of alloreactive murine cytotoxic T-lymphocytes in vivo.
Five different beta(1 leads to 3) glucans were tested for immune adjuvant activity on the in vivo induction of alloreactive murine cytotoxic T-lymphocytes (CTL). The beta(1 leads to 3) glucans, lentinan, pachyman, pachymaran, and two differently substitute hydroxyethylated pachymans strongly enhanced the in vivo generation of alloreactive CTL. The augmenting effect of i.p.-administered beta(1 leads to 3) glucans exhibited a clear dose-response relationship and was strictly dependent on the injection schedule used. Injection of high doses of beta(1 leads to 3) glucans as well as the injection during the late phase of the immune response markedly suppressed the magnitude of the lytic CTL activity induced. When the optimal conditions for enhanced CTL responses were chosen, the augmented CTL activity within spleen cells and mesenteric lymph node cells persisted for more than 25 days. Since beta(1 leads to 3) glucans are chemically defined substances without obvious toxic side effects, they may be of potential use to augment in vivo antigen-specific T-cell responses. (+info)
Lentinula edodes tlg1 encodes a thaumatin-like protein that is involved in lentinan degradation and fruiting body senescence.
Lentinan is an antitumor product that is purified from fresh Lentinula edodes fruiting bodies. It is a cell wall component, comprising beta-1,3-glucan with beta-1,6-linked branches, which becomes degraded during postharvest preservation as a result of increased glucanase activity. In this study, we used N-terminal amino acid sequence to isolate tlg1, a gene encoding a thaumatin-like (TL) protein in L. edodes. The cDNA clone was approximately 1.0 kb whereas the genomic sequence was 2.1 kb, and comparison of the two indicated that tlg1 contains 12 introns. The tlg1 gene product (TLG1) was predicted to comprise 240 amino acids, with a molecular mass of 25 kD and isoelectric point value of 3.5. The putative amino acid sequence exhibits approximately 40% identity with plant TL proteins, and a fungal genome database search revealed that these TL proteins are conserved in many fungi including the basidiomycota and ascomycota. Transcription of tlg1 was not detected in vegetative mycelium or young and fresh mushrooms. However, transcription increased following harvest. Western-blot analysis demonstrated a rise in TLG1 levels following harvest and spore diffusion. TLG1 expressed in Escherichia coli and Aspergillus oryzae exhibited beta-1,3-glucanase activity and, when purified from the L. edodes fruiting body, demonstrated lentinan degrading activity. Thus, we suggest that TLG1 is involved in lentinan and cell wall degradation during senescence following harvest and spore diffusion. (+info)
A case of recurrent ovarian cancer successfully treated with adoptive immunotherapy and lentinan.
BACKGROUND: Immunotherapy is useful for the prevention of the post-operative recurrence of some types of cancer and, in combination with certain anticancer drugs, is expected to prolong survival time. However, the clinical efficacy of immunotherapy alone against advanced cancer has not yet been demonstrated. CASE REPORT: A 67-year-old woman with ovarian cancer who had undergone post-operative adjuvant chemotherapy suffered from recurrent cancer in the lymph nodes. A partial response to adoptive immunotherapy and the administration of the biological response modifier, lentinan containing beta-glucan as the principal component, was maintained for five months without the use of chemotherapy. CONCLUSION: Adoptive immunotherapy with lentinan alone was potentially useful for the treatment of lymph node metastases from ovarian cancer. (+info)
Cancer chronomics III. Chronomics for cancer, aging, melatonin and experimental therapeutics researchers.
This position paper documents the merit of including for basic and clinical investigations the mapping of circadian and other rhythms and yet broader chronomes, time structures in and around us. Chronobiometry used herein relies on inferential statistical methods and on materials documented earlier. The circadian amplitude of melatonin is shown to relate both to cancer risk and to the presence of overt cancer, when no differences are found in the 24-hour average of melatonin. Optimization of treatment by timing, thoroughly documented along the circadian scale earlier, could be broadened to include optimization along the scale of the week, and eventually beyond. In both cases, reliance on marker rhythmometry is advocated. More generally, the limits of knowledge are expanded by considering already mapped spectral components and their characteristics that can be influenced by the dynamics of heliogeomagnetic signals heretofore unassessed. (+info)
Efficacy of orally administered superfine dispersed lentinan (beta-1,3-glucan) for the treatment of advanced colorectal cancer.
BACKGROUND: Lentinan (LNT) is an immune adjuvant medicine for advanced gastric cancer in Japan. Recently, an oral formulation of superfine dispersed lentinan (SDL) has become clinically available. To investigate the safety and effectiveness of SDL, a multi center clinical study in patients with advanced colorectal cancer was conducted. PATIENTS AND METHODS: Adverse events were assessed and the patients' quality of life (QOL) and the binding ability of peripheral blood monocytes (PBM) to LNT were also evaluated. RESULTS: Four grade 2 adverse events associated with SDL treatment were observed among the 80 patients. Adverse events associated with chemotherapy were observed in 9 out of the 64 chemotherapy-treated patients. Among the 48 patients assessed for QOL, the patients with low QOL scores before SDL treatment (n=23) reported a significant improvement in their QOL scores after 12 weeks of SDL administration. The rates of LNT-binding PBM in the QOL-improved group were significantly higher than those in the QOL-not-improved group (p<0.05). CONCLUSION: SDL was safe and effective for suppressing the adverse effects of chemotherapy as well as improving QOL. The binding ability of PBM to LNT appears to be a promising predictor of QOL improvement after SDL administration. (+info)
Individual patient based meta-analysis of lentinan for unresectable/recurrent gastric cancer.
BACKGROUND: In the present study, the effect of immunochemotherapy with lentinan compared with that of chemotherapy alone was evaluated in patients with advanced gastric cancer through individual patient data (IPD) meta-analysis. MATERIALS AND METHODS: Based on a computerized and manual search, all eligible centrally randomized controlled trials (RCT) which compared chemotherapy regimens with or without lentinan administration for advanced gastric cancer patients were included. RESULTS: In total, 650 IPD from 5 trials were available. Lentinan significantly prolonged the overall survival (stratified log-rank p=0.011). The overall hazard ratio (HR) was 0.80 (95% confidence interval=0.68-0.95) and there was no heterogeneity between trials. Additionally, lentinan was possibly more effective in patients with lymph-node metastasis than in non-node metastasis patients (P for interaction=0.077). CONCLUSION: The addition of lentinan to standard chemotherapy offers a significant advantage over chemotherapy alone in terms of survival for patients with advanced gastric cancer. (+info)