Immunomodulatory effects of the botanical compound LCS101: implications for cancer treatment.

OBJECTIVE: To examine the effects of LSC101, a botanical compound, on adaptive and innate immunity. MATERIALS AND METHODS: LCS101 preparations were tested for batch-to-batch consistency using high-performance liquid chromatography. T-cell activation was quantified in murine spleen cells using 3H-thymidine incorporation, and cytokine production analyzed with enzyme-linked immunosorbent assay. Natural killer cell activity was tested on human blood cells using flow cytometry, and cytotoxicity measured by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide and apoptosis using a FACSCalibur. Effects on interferon-γ production in fluorouracil/doxorubicin-treated mice were tested with enzyme-linked immunosorbent assay. RESULTS: High-performance liquid chromatography analysis demonstrated batch-to-batch consistency. T-cell proliferation was increased, and a dose-dependent activation of natural killer cells and macrophage tumor necrosis factor-α secretion were observed with LCS101 treatment. Interferon-γ levels, reduced following fluorouracil treatment, were corrected in treated animals. No toxicity or compromised treatment outcomes were associated with LCS101 exposure. CONCLUSIONS: LCS101 demonstrated significant effects on a number of immune processes. Further research is needed in order to understand the molecular immunomodulatory pathways affected by this compound, as well as clinical implications for treatment.

A prospective, controlled study of the botanical compound mixture LCS101 for chemotherapy-induced hematological complications in breast cancer.

BACKGROUND: This prospective, controlled study evaluated the safety, tolerability, and efficacy of the mixture of botanical compounds known as LCS101 in preventing chemotherapy-induced hematological toxicity in breast cancer patients. METHODS: Female patients diagnosed with localized breast cancer were randomly allocated to receive treatment with either LCS101 or placebo capsules, in addition to conventional chemotherapy. The study intervention was initiated 2 weeks prior to the initiation of chemotherapy and continued until chemotherapy was completed, with participants receiving 2 g of LCS101 capsules thrice daily. Subjects were assessed for the development of hematological and nonhematological toxicities, as well as the tolerability and safety of the study intervention. RESULTS: Sixty-five breast cancer patients were recruited, with 34 allocated to LCS101 and 31 allocated to placebo treatment. Patients in the treatment group developed significantly less severe (grades 2-4) anemia (p < .01) and leukopenia (p < .03) when comparing grades 0-1 with grades 2-4, with significantly less neutropenia (p < .04) when comparing grades 0-2 with grades 3-4. This effect was more significant among patients undergoing a dose-dense regimen. No statistically significant effect was found with respect to nonhematological toxicities, and side effect rates were not significantly different between the groups, with no severe or life-threatening events observed in either group. CONCLUSION: The addition of LCS101 to anthracycline- and taxane-based chemotherapy is safe and well tolerated, and may significantly prevent some chemotherapy-induced hematological toxicities in early breast cancer patients. These results should encourage further larger and more extensive clinical trials.

Applying principles from complex systems to studying the efficacy of CAM therapies.

In October 2007, a National Center for Complementary and Alternative Medicine (NCCAM)-sponsored workshop, entitled "Applying Principles from Complex Systems to Studying the Efficacy of CAM Therapies," was held at Georgetown University in Washington, DC. Over a 2-day period, the workshop engaged a small group of experts from the fields of complementary and alternative medicine (CAM) research and complexity science to discuss and examine ways in which complexity science can be applied to CAM research. After didactic presentations and small-group discussions, a number of salient themes and ideas emerged. This paper article describes the workshop program and summarizes these emergent ideas, which are divided into five broad categories: (1) introduction to complexity; (2) challenges to CAM research; (3) applications of complexity science to CAM; (4) CAM as a model of complexity applied to medicine; and (5) future directions. This discusses possible benefits and challenges associated with applying complexity science to CAM research. By providing an introductory framework for this collaboration and exchange, it is hoped that this article may stimulate further inquiry into this largely unexplored area of research.

Survival impact of integrative cancer care in advanced metastatic breast cancer.

Integrative cancer treatment is of substantial interest to many cancer patients. Research is needed to evaluate the effects of integrative treatment on patient outcomes. We report survival data for a consecutive case series of advanced metastatic breast cancer patients who received a comprehensive clinical program combining conventional treatments with nutrition and supplementation, fitness and mind-spirit instruction at the Block Center for Integrative Cancer Treatment. Treatment outcomes using integrative care for this disease have not previously been documented; survival data will thus contribute to decisions concerning future research directions and design. Ninety consecutive patients with metastatic breast cancer diagnosed during 1984-1997 who received chemotherapy at the integrative cancer center were included. Prognostic factors, treatments and survival from onset of metastases were determined from analysis of scans, labs, pathology and medical records. The log-rank test and Cox proportional hazards analyses were used, and a Kaplan-Meier curve was calculated. All patients had metastatic disease at baseline, 96% were relapsed and 52% had received prior chemotherapy for metastatic disease. Median age at onset of metastasis was 46 years. Median survival was 38 months (95% CI 27,48). Published literature on populations with somewhat more favorable prognostic factors treated in conventional clinics showed median survivals of 20 to 23 months. Through the 1990s, median survival reported in metastatic breast cancer trials or observations generally ranged from 12 to 24 months. Five-year survival was 27% for Center versus 17% for comparison patients. Despite a higher proportion of younger and relapsed patients, survival of metastatic breast cancer patients at the Center was approximately double that of comparison populations and possibly even higher compared to trials published during this period. Explanations for the advantage relative to conventional treatment alone may include the nutritional, nutraceutical, exercise and psychosocial interventions, individually or in combination; self-selection of patients cannot be ruled out. Further research to evaluate the impact of integrative breast cancer treatment on survival is warranted.

Delta 9-tetrahydrocannabinol inhibits cell cycle progression by downregulation of E2F1 in human glioblastoma multiforme cells.

BACKGROUND: The active components of Cannabis sativa L., Cannabinoids, traditionally used in the field of cancer for alleviation of pain, nausea, wasting and improvement of well-being have received renewed interest in recent years due to their diverse pharmacologic activities such as cell growth inhibition, anti-inflammatory activity and induction of tumor regression. Here we used several experimental approaches, which identified delta-9-tetrahydrocannabinol (Delta(9)-THC) as an essential mediator of cannabinoid antitumoral action. METHODS AND RESULTS: Administration of Delta(9)-THC to glioblastoma multiforme (GBM) cell lines results in a significant decrease in cell viability. Cell cycle analysis showed G(0/1) arrest and did not reveal occurrence of apoptosis in the absence of any sub-G(1) populations. Western blot analyses revealed a THC altered cellular content of proteins that regulate cell progression through the cell cycle. The cell content of E2F1 and Cyclin A, two proteins that promote cell cycle progression, were suppressed in both U251-MG and U87-MG human glioblastoma cell lines, whereas the level of p16(INK4A), a cell cycle inhibitor was upregulated. Transcription of thymidylate synthase (TS) mRNA, which is promoted by E2F1, also declined as evident by QRT-PCR. The decrease in E2F1 levels resulted from proteasome mediated degradation and was prevented by proteasome inhibitors. CONCLUSIONS: Delta(9)-THC is shown to significantly affect viability of GBM cells via a mechanism that appears to elicit G(1) arrest due to downregulation of E2F1 and Cyclin A. Hence, it is suggested that Delta(9)-THC and other cannabinoids be implemented in future clinical evaluation as a therapeutic modality for brain tumors.