Jillian L. Capodice

Randomized, Blinded, Sham-Controlled Trial of Acupuncture for the Management of Aromatase Inhibitor–Associated Joint Symptoms in Women With Early-Stage Breast Cancer

PURPOSE Women with breast cancer (BC) treated with aromatase inhibitors (AIs) may experience joint symptoms that can lead to discontinuation of effective therapy. We examined whether acupuncture improves AI-induced arthralgias in women with early-stage BC. METHODS We conducted a randomized, controlled, blinded study comparing true acupuncture (TA) versus sham acupuncture (SA) twice weekly for 6 weeks in postmenopuasal women with BC who had self-reported musculoskeletal pain related to AIs. TA included full body/auricular acupuncture and joint-specific point prescriptions, whereas SA involved superficial needle insertion at nonacupoint locations. Outcome measures included the Brief Pain Inventory-Short Form (BPI-SF), Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), and Modified Score for the Assessment of Chronic Rheumatoid Affections of the Hands (M-SACRAH) obtained at baseline and at 3 and 6 weeks. Results Of 51 women enrolled, 43 women were randomly assigned and 38 were evaluable. Baseline characteristics were comparable between the two groups. Our primary end point was the difference in mean BPI-SF worst pain scores at 6 weeks, which was lower for TA compared with SA (3.0 v 5.5; P < .001). We also found differences between TA and SA in pain severity (2.6 v 4.5; P = .003) and pain-related interference (2.5 v 4.5; P = .002) at 6 weeks. Similar findings were seen for the WOMAC and M-SACRAH scores. The acupuncture intervention was well-tolerated. CONCLUSION Women with AI-induced arthralgias treated with TA had significant improvement of joint pain and stiffness, which was not seen with SA. Acupuncture is an effective and well-tolerated strategy for managing this common treatment-related side effect.

Evidence-based clinical practice guidelines for integrative oncology: complementary therapies and botanicals.

In recent years, the term integrative medicine has gained acceptance in medical academia. The Consortium of Academic Health Centers for Integrative Medicine defi nes this term as “the practice of medicine that reaffi rms the importance of the relationship between practitioner and patient, focuses on the whole person, is informed by evidence, and makes use of all appropriate therapeutic approaches, healthcare professionals, and disciplines to achieve optimal health and healing.” 1 Integrative oncology has been specifi cally described as both a science and a philosophy that focuses on the complex health of people with cancer and proposes an array of approaches to accompany the conventional therapies of surgery, chemotherapy, molecular therapeutics, and radiotherapy to facilitate health. 2 The SIO and its Medline -indexed journal ( Journal of the Society of Integrative Oncology ), founded by leading oncologists and oncology professionals from major cancer centers and organizations, promote quality research and appropriate application of useful, adjunctive complementary modalities T he Society for Integrative Oncology (SIO) is an international organization dedicated to encouraging scientifi c evaluation, dissemination of evidence-based information, and appropriate clinical integration of complementary therapies. Practice guidelines have been developed by the authors and endorsed by the Executive Committee of the SIO. Guidelines are a work in progress; they will be updated as needed and are available on the SIO Web site ().

A pilot study on acupuncture for lower urinary tract symptoms related to chronic prostatitis/chronic pelvic pain

BackgroundThe etiology and treatment of chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) remain poorly understood. Pain, lower urinary tract voiding symptoms and negative impact on quality of life (QOL) are the most common complaints. Acupuncture, which has been widely used to treat painful and chronic conditions, may be a potential treatment to alleviate the constellation of symptoms experienced by men with CP/CPPS. The purpose of our study was to assess the impact of standardized full body and auricular acupuncture in men refractory to conventional therapies and collect pilot data to warrant further randomized trials.MethodsTen men diagnosed with category IIIA or IIIB CP/CPPS >6 months, refractory to at least 1 conventional therapy (antibiotics, anti-inflammatory agents, 5-α reductase inhibitors, α-1 blockers) and scoring >4 on the pain subset of the NIH-CPSI were prospectively analyzed in an Institutional Review Board (IRB) approved, single-center clinical trial (Columbia University Medical Center IRB#AAAA-7460). Standardized full body and auricular acupuncture treatment was given twice weekly for 6 weeks. The primary endpoints were total score of the NIH-CPSI and assessment of serious adverse events. The secondary endpoints were individual scores of the NIH-CPSI and QOL questionnaire scores of the short-form 36 (SF-36).ResultsThe median age of the subjects was 36 years (range 29–63). Decreases in total NIH-CPSI scores (mean ± SD) after 3 and 6 weeks from baseline (25.1 ± 6.6) were 17.6 ± 5.7 (P < 0.006) and 8.8 ± 6.2 (P < 0.006) respectively and remained significant after an additional 6 weeks of follow-up (P < 0.006). Symptom and QOL/NIH-CPSI sub-scores were also significant (P < 0.002 and P < 0.002 respectively). Significance in 6 of 8 categories of the SF-36 including bodily pain (P < 0.002) was achieved. One regression in the SF-36 vitality category was observed after follow-up. There were no adverse events.ConclusionThe preliminary findings, although limited, suggest the potential therapeutic role of acupuncture in the treatment of CP/CPPS. Data from this and previous studies warrant randomized trials of acupuncture for CP/CPPS and particular attention towards acupuncture point selection, treatment intervention, and durability of acupuncture.

A Concentrated Aglycone Isoflavone Preparation (GCP) That Demonstrates Potent Anti-Prostate Cancer Activity In vitro and In vivo

Purpose: Isoflavones have anticancer activities, but naturally occurring isoflavones are predominantly glycosylated and poorly absorbed. Genistein combined polysaccharide (GCP; Amino Up Chemical Co., Sapporo, Japan), is a fermentation product of soy extract and basidiomycetes mycillae that is enriched in biologically active aglycone isoflavones. This study analyzes GCP in vitro and in vivo for potential utility as a prostate cancer chemopreventative agent. Experimental Design: Androgen-sensitive LNCaP and androgen-independent PC-3 cells were grown with various concentrations of GCP. In vitro cell growth was analyzed by the WST-1 assay, and apoptosis was assessed by fluorescence-activated cell sorting and detection of poly(ADP-ribose) polymerase cleavage using Western blot techniques. Effects of GCP on expression of cell cycle-regulatory proteins p53 (LNCaP only), p21, and p27 and the protein kinase Akt were considered using Western blot techniques. An in vivo LNCaP xenograft model was used to study the effects of a 2% GCP-supplemented diet on tumor growth in comparison with a control diet. Results: GCP significantly suppressed LNCaP and PC-3 cell growth over 72 h (89% and 78% in LNCaP and PC-3, respectively, at 10 μg/ml; P < 0.0001). This reduction was associated with apoptosis in LNCaP cells, but not in PC-3 cells. GCP induced p27 and p53 (LNCaP only) protein expression within 6 h and suppressed phosphorylated Akt in both cell lines. The 2% GCP-supplemented diet significantly slowed LNCaP tumor growth, increasing apoptosis (P < 0.001), and decreasing proliferation (P < 0.001) over 4 weeks. Conclusions: GCP has potent growth-inhibitory effects against prostate cancer cell lines in vitro and in vivo. These data suggest GCP has potential as an effective chemopreventive agent against prostate cancer cell growth.

Zyflamend, a unique herbal preparation with nonselective COX inhibitory activity, induces apoptosis of prostate cancer cells that lack COX-2 expression.

Abstract: Cyclooxygenase (COX) inhibitors have suppressive effects on several types of cancer cells including prostate cancer. In this study, we considered the potential COX-inhibitory activity of a unique anti-inflammatory herbal preparation (Zyflamend®; New Chapter, Inc., Brattleboro, VT) and analyzed its effects on the human prostate cancer cell line LNCaP. COX inhibitory activity of Zyflamend was determined by a spectrophotometric-based assay using purified ovine COX-1 and COX-2 enzymes. Effects of Zyflamend on LNCaP cell growth and apoptosis in vitro were assessed by cell counting, Western blot detection of poly ADP-ribose polymerase (PARP) cleavage, and measurement of caspase-3 activity in treated and control cell extracts. Western blotting techniques were conducted to determine the effects of this herbal preparation on the expression of the cell signaling proteins, p21, androgen receptor (AR), phospho-protein kinase C (pPKC)α/β, and phospho (p)Stat3. The phospohorylation status of several signal transduction phosphoproteins was profiled using a high-throughput phosphoprotein screening assay in treated cells and compared to controls. Zyflamend dramatically decreased COX-1 and COX-2 enzymatic activity. Elevated p21 expression coincided with attenuated cell growth following treatment of LNCaP cells with Zyflamend. PARP cleavage fragments were evident, and caspase-3 activity was upregulated over the control indicating the ability of Zyflamend to induce apoptosis of these cells. Androgen receptor expression levels declined by 40%, and decreases were observed in the active forms of Stat3 and PKCα/β in Zyflamend-treated LNCaP cells. Zyflamend inhibited both COX-1 and COX-2 enzymatic activities, suppressed cell growth, and induced apoptosis in LNCaP cells. However, our data suggests that the effects are likely due to COX-independent mechanisms potentially involving enhanced expression of p21 and reduced expression of AR, pStat3, and pPKCα/β.

COMPLEMENTARY AND ALTERNATIVE MEDICINE FOR CHRONIC PROSTATITIS/CHRONIC PELVIC PAIN SYNDROME

To discuss challenges concerning treatment for chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) and review complementary and alternative medical (CAM) therapies being evaluated for this condition, we performed a comprehensive search of articles published from 1990–2005 using the PubMed, Medline databases. Data from the articles were abstracted and pooled by subject. Keywords cross-searched with CP/CPPS included: complementary, alternative, integrative, therapies, interventions, nutrition, antioxidants, herbs, supplements, biofeedback and acupuncture. Listed articles with no abstracts were not included. Various CAM therapies for CP/CPPS exist including biofeedback, acupuncture, hyperthermia and electrostimulation. Additionally, a variety of in vitro and in vivo studies testing herbal and nutritional supplements were found. Saw palmetto, cernilton and quercetin were the most frequently tested supplements for CP/CPPS. Although many CAM therapies demonstrate positive preliminary observations as prospective treatments for CP/CPPS, further exploratory studies including more randomized, controlled trials are necessary for significant validation as treatment options for this complex disorder.

Integrating Dietary Supplements Into Cancer Care

Many studies confirm that a majority of patients undergoing cancer therapy use self-selected forms of complementary therapies, mainly dietary supplements. Unfortunately, patients often do not report their use of supplements to their providers. The failure of physicians to communicate effectively with patients on this use may result in a loss of trust within the therapeutic relationship and in the selection by patients of harmful, useless, or ineffective and costly nonconventional therapies when effective integrative interventions may exist. Poor communication may also lead to diminishment of patient autonomy and self-efficacy and thereby interfere with the healing response. To be open to the patient’s perspective, and sensitive to his or her need for autonomy and empowerment, physicians may need a shift in their own perspectives. Perhaps the optimal approach is to discuss both the facts and the uncertainty with the patient, in order to reach a mutually informed decision. Today’s informed patients truly value physicians who appreciate them as equal participants in making their own health care choices. To reach a mutually informed decision about the use of these supplements, the Clinical Practice Committee of The Society of Integrative Oncology undertook the challenge of providing basic information to physicians who wish to discuss these issues with their patients. A list of leading supplements that have the best suggestions of benefit was constructed by leading researchers and clinicians who have experience in using these supplements. This list includes curcumin, glutamine, vitamin D, Maitake mushrooms, fish oil, green tea, milk thistle, Astragalus, melatonin, and probiotics. The list includes basic information on each supplement, such as evidence on effectiveness and clinical trials, adverse effects, and interactions with medications. The information was constructed to provide an up-to-date base of knowledge, so that physicians and other health care providers would be aware of the supplements and be able to discuss realistic expectations and potential benefits and risks.

Zyflamend inhibits the expression and function of androgen receptor and acts synergistically with bicalutimide to inhibit prostate cancer cell growth

Interference of androgen receptor (AR) signaling is a target for prostate cancer (CaP) chemoprevention and treatment. We hypothesize that Zyflamend (ZYF) assert its anti‐cancer effect by disrupting AR signaling. We also hypothesize that it may act synergistically with the anti‐androgen bicalutimde to inhibit CaP cell growth.

The use of herbal and over-the-counter dietary supplements for the prevention of prostate cancer

Having a high probability of experiencing prostate cancer during their lifetime, men are increasingly seeking protection against this disease with the use of over-the-counter dietary supplements containing herbs, vitamins, or plantderived biochemical agents. The use of these agents for prostate cancer prevention is driven by epidemiology supporting the idea that regional diets and consumption of specific dietary components (certain herbs, vitamins, isoflavones, and polyphenols) are associated with a lower risk for prostate cancer, in conjunction with basic research that is defining molecules within food substances that kill or suppress growth of cultured human prostate cancer cells. Moreover, there is a sense that these dietary agents lack side effects, although this assumption often is faulty. Unfortunately, at this time, there is insufficient clinical evidence to support the widespread use of these dietary supplements for chemoprevention of prostate cancer, although ongoing clinical trials of the most promising vitamins and minerals are approaching conclusion.

Acupuncture in the Oncology Setting: Clinical Trial Update

Opinion statementAcupuncture, the insertion of sterile needles into acupuncture points of traditional meridians on the body, is a common and effective treatment for a number of supportive care issues in oncology including acute chemotherapy-induced nausea and vomiting. In the Integrative Oncology setting, acupuncture and Traditional Oriental Medicine have become more visible and many oncology clinics, academic health centers and comprehensive cancer centers recommend and administer acupuncture treatment. Continued basic studies on the physiologic mechanisms of acupuncture and recent clinical trials of acupuncture for cancer patients are enhancing our knowledge and informing our guidelines. While debates on methodological problems confronting the study of acupuncture remain, the most recent research demonstrates that acupuncture is safe, tolerable and effective for a range of side effects resulting from conventional cancer treatments.