Background Cancer patients commonly use dietary supplements to “boost immune function”. A polysaccharide extract from Grifola frondosa (Maitake extract) showed immunomodulatory effects in preclinical studies and therefore the potential for clinical use. Whether oral administration in human produces measurable immunologic effects, however, is unknown. Methods In a phase I/II dose escalation trial, 34 postmenopausal breast cancer patients, free of disease after initial treatment, were enrolled sequentially in five cohorts. Maitake liquid extract was taken orally at 0.1, 0.5, 1.5, 3, or 5 mg/kg twice daily for 3 weeks. Peripheral blood was collected at days −7, 0 (prior to the first dosing), 7, 14, and 21 for ex vivo analyses. The primary endpoints were safety and tolerability. Results No dose-limiting toxicity was encountered. Two patients withdrew prior to completion of the study due to grade I possibly related side effects: nausea and joint swelling in one patient; rash and pruritus in the second. There was a statistically significant association between Maitake and immunologic function (p < 0.0005). Increasing doses of Maitake increased some immunologic parameters and depressed others; the dose–response curves for many endpoints were non-monotonic with intermediate doses having either immune enhancing or immune suppressant effects compared with both high and low doses. Conclusions Oral administration of a polysaccharide extract from Maitake mushroom is associated with both immunologically stimulatory and inhibitory measurable effects in peripheral blood. Cancer patients should be made aware of the fact that botanical agents produce more complex effects than assumed, and may depress as well as enhance immune function.

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Background Higher serum 25-hydroxy vitamin D [25(OH)D] levels are associated with decreased colorectal cancer (CRC) incidence. In this retrospective study of stage IV CRC patients, we evaluate whether 25(OH)D levels at diagnosis correlate with survival. Methods Stored sera from carcinoembryonic antigen (CEA) measurements obtained between February 2005 and March 2006 were screened. The first 250 patients with CEA ±30 days of stage IV CRC diagnosis were included. Serum 25(OH)D levels were determined and categorized as adequate ≥30 ng/mL, or deficient <30 ng/mL. Multivariable Cox regression models controlling for albumin and Eastern Cooperative Oncology Group performance status were used to investigate whether higher 25(OH)D levels were associated with prolonged survival. Results A total of 207 patients (83%) were vitamin D-deficient (median, 21 ng/mL), with deficiencies significantly more likely among non-Hispanic black patients (P=0.009). Higher levels were associated with prolonged survival in categorical variable analysis: adequate vs deficient, hazard ratio 0.61, 95% CI 0.38–0.98, P=0.041. Conclusions A majority of newly diagnosed stage IV CRC patients are vitamin D-deficient. Our data suggest that higher 25(OH)D levels are associated with better overall survival. Clinical trials to determine whether aggressive vitamin D repletion would improve outcomes for vitamin D-deficient CRC patients are warranted.

BackgroundMyelodysplastic syndromes (MDS) are characterized by ineffective erythropoiesis with dysplastic bone marrow leading to peripheral cytopenia, risk of infection, and progression to acute myelogenous leukemia. Maitake mushroom beta-glucan, a dietary supplement, stimulates hematopoietic progenitor cell differentiation, granulocyte colony-stimulating factor production, and recovery of peripheral blood leukocytes after bone marrow injury. This phase II trial examined the effects of Maitake on innate immune function in MDS.MethodsMyelodysplastic syndromes patients with International Prognostic Scoring System Low- and Intermediate-1-risk disease received oral Maitake extract at 3 mg/kg twice daily for 12 weeks. Primary endpoints included neutrophil count and function tested as endogenous or stimulated neutrophil production of reactive oxygen species (ROS) by flow cytometry compared with age-matched healthy controls (HC). ROS activators were Escherichiacoli, phorbol ester, and the bacterial peptide N-formylmethionyl-leucyl-phenylalanine (fMLP). Complete blood counts, chemistry panels, iron studies, and monocyte function were evaluated.ResultsOf 21 patients enrolled, 18 completed the study and were evaluable. Maitake increased endogenous (basal) neutrophil (p = 0.005) and monocyte function (p = 0.021). Pre-treatment monocyte response to E. coli was reduced in MDS patients compared with HC (p = 0.002) and increased (p = 0.0004) after treatment. fMLP-stimulated ROS production response also increased (p = 0.03). Asymptomatic eosinophilia occurred in 4 patients (p = 0.014). Other changes in albumin, hemoglobin, and total protein were not clinically relevant.ConclusionsMaitake was well tolerated. Enhanced in vitro neutrophil and monocyte function following treatment demonstrate that Maitake has beneficial immunomodulatory potential in MDS. Further study is warranted.

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Bone marrow myelotoxicity is a major limitation of chemotherapy. While granulocyte colony stimulating factor (G-CSF) treatment is effective, alternative approaches to support hematopoietic recovery are sought. We previously found that a beta-glucan extract from maitake mushroom Grifola frondosa (MBG) enhanced colony forming unit-granulocyte monocyte (CFU-GM) activity of mouse bone marrow and human hematopoietic progenitor cells (HPC), stimulated G-CSF production and spared HPC from doxorubicin toxicity in vitro. This investigation assessed the effects of MBG on leukocyte recovery and granulocyte/monocyte function in vivo after dose intensive paclitaxel (Ptx) in a normal mouse. After a cumulative dose of Ptx (90–120 mg/kg) given to B6D2F1 mice, daily oral MBG (4 or 6 mg/kg), intravenous G-CSF (80 μg/kg) or Ptx alone were compared for effects on the dynamics of leukocyte recovery in blood, CFU-GM activity in bone marrow and spleen, and granulocyte/monocyte production of reactive oxygen species (ROS). Leukocyte counts declined less in Ptx + MBG mice compared to Ptx-alone (p = 0.024) or Ptx + G-CSF treatment (p = 0.031). Lymphocyte levels were higher after Ptx + MBG but not Ptx + G-CSF treatment compared to Ptx alone (p < 0.01). MBG increased CFU-GM activity in bone marrow and spleen (p < 0.001, p = 0.002) 2 days after Ptx. After two additional days (Ptx post-day 4), MBG restored granulocyte/monocyte ROS response to normal levels compared to Ptx-alone and increased ROS response compared to Ptx-alone or Ptx + G-CSF (p < 0.01, both). The studies indicate that oral MBG promoted maturation of HPC to become functionally active myeloid cells and enhanced peripheral blood leukocyte recovery after chemotoxic bone marrow injury.

Patients with leukemia often seek additional treatments not prescribed by their oncologist in an effort to improve their cancer treatment outcome or to manage symptoms. Complementary therapies are used in conjunction with traditional cancer treatments to decrease symptoms and side effects associated with cancer or cancer treatment, and to improve patients’ overall quality of life. Complementary therapies are distinct from so-called ‘alternative’ therapies, which are unproven, ineffective and may postpone or interfere with mainstream cancer treatment. Complementary therapies are pleasant, inexpensive, nonpharmacologic and effective. For patients with leukemia, the complementary therapies that are always appropriate include mind–body interventions, such as self-hypnosis, meditation, guided imagery and breath awareness. Massage and reflexology (foot massage) decrease symptoms with effects lasting at least 2 days following treatment. Acupuncture is very beneficial for symptom management without adverse consequences. Physical fitness with regular exercise and healthy dietary habits can significantly decrease side effects of cancer treatments and may prolong survival. Botanical extracts and vitamin supplements may interfere with active cancer treatments, and should be discussed with the oncologist or pharmacist before use.

The findings suggest that an inflammatory process plays a role in at least some cases of Sneddon's syndrome.