Integrative Cancer Therapies recent issues

In This Issue

Block, K. I. — Thu, 08 Oct 2009 04:26:33 PDT

Could Integrative Cancer Treatment be Cost-Saving and Resuscitate a Submerged Medical System?

Block, K. I. — Thu, 08 Oct 2009 04:26:33 PDT

Drug--Botanical Interactions: A Review of the Laboratory, Animal, and Human Data for 8 Common Botanicals

Shord, S. S., Shah, K., Lukose, A. — Thu, 08 Oct 2009 04:26:33 PDT

Many Americans use complementary and alternative medicine (CAM) to prevent or alleviate common illnesses, and these medicines are commonly used by individuals with cancer.These medicines or botanicals share the same metabolic and transport proteins, including cytochrome P450 enzymes (CYP), glucuronosyltransferases (UGTs), and P-glycoprotein (Pgp), with over-the-counter and prescription medicines increasing the likelihood of drug—botanical interactions.This review provides a brief description of the different proteins, such as CYPs, UGTs, and Pgp.The potential effects of drug—botanical interactions on the pharmacokinetics and pharmacodynamics of the drug or botanical and a summary of the more common models used to study drug metabolism are described.The remaining portion of this review summarizes the data extracted from several laboratory, animal, and clinical studies that describe the metabolism, transport, and potential interactions of 8 selected botanicals. The 8 botanicals include black cohosh, Echinacea, garlic, Gingko biloba, green tea, kava, milk thistle, and St John’s wort; these botanicals are among some of the more common botanicals taken by individuals with cancer.These examples are included to demonstrate how to interpret the different studies and how to use these data to predict the likelihood of a clinically significant drug—botanical interaction.

A Randomized Controlled Trial of the Effects of Transcendental Meditation on Quality of Life in Older Breast Cancer Patients

Thu, 08 Oct 2009 04:26:33 PDT

This single-blind, randomized controlled trial evaluated the impact of the Transcendental Meditation program plus standard care as compared with standard care alone on the quality of life (QOL) of older women (≥55 years) with stage II to IV breast cancer. One hundred and thirty women (mean age = 63.8) were randomly assigned to either experimental (n = 64) or control (n = 66) groups. Functional Assessment of Cancer Therapy—Breast (FACT-B), Functional Assessment of Chronic Illness Therapy— Spiritual Well-Being (FACIT-SP), and Short-Form (SF)-36 mental health and vitality scales were administered every 6 months over an average 18-month intervention period. Significant improvements were found in the Transcendental Meditation group compared with controls in overall QOL, measured by the FACT-B total score (P = .037), emotional well-being (P = .046), and social well-being (P = .003) subscales, and SF-36 mental health ( P = .017). Results indicate that the Transcendental Meditation technique improves the QOL of older breast cancer patients. It is recommended that this stress reduction program, with its ease of implementation and home practice, be adopted in public health programs.

Integrative Tumor Board: A Case Report and Discussion From Dana-Farber Cancer Institute

Thu, 08 Oct 2009 04:26:33 PDT

A 34-year-old woman carrying a BRCA1 gene and a significant family history was diagnosed with T1c, N1 breast cancer. The tumor was estrogen receptor, progesterone receptor, and HER-2/Neu negative.The patient received dose-dense chemotherapy with Adriamycin and Cytoxan followed by Taxol, and left breast irradiation. Later, a bilateral S-GAP flap reconstruction with right prophylactic mastectomy and left mastectomy were performed. During her treatment, the patient had an integrative medicine consultation and was seen by a team of health care providers specializing in integrative therapies, including integrative nutrition, therapeutic massage, acupuncture, and yoga. Each modality contributed unique benefit in her care that led to a satisfactory outcome for the patient.A detailed discussion regarding her care from each modality is presented.The case elucidates the need for integrative approaches for cancer patients in a conventional medical setting.

Pomegranate Fruit Extract Impairs Invasion and Motility in Human Breast Cancer

Thu, 08 Oct 2009 04:26:33 PDT

Purpose. Pomegranate fruit extracts (PFEs) possess polyphenolic and other compounds with antiproliferative, pro-apoptotic and anti-inflammatory effects in prostate, lung, and other cancers. Because nuclear transcription factor-kB (NF-kB) is known to regulate cell survival, proliferation, tumorigenesis, and inflammation, it was postulated that PFEs may exert anticancer effects at least in part by modulating NF-kB activity. Experimental design. The authors investigated the effect of a novel, defined PFE consisting of both fermented juice and seed oil on the NF-kB pathway, which is constitutively active in aggressive breast cancer cell lines. The effects of the PFE on NF-kB—regulated cellular processes such as cell survival, proliferation, and invasion were also examined. Results. Analytical characterization of the bioactive components of the PFE revealed active constituents, mainly ellagitannins and phenolic acids in the aqueous PFE and conjugated octadecatrienoic acids in the lipid PFE derived from seeds.The aqueous PFE dose-dependently inhibited NF-kB—dependent reporter gene expression associated with proliferation, invasion, and motility in aggressive breast cancer phenotypes while decreasing RhoC and RhoA protein expression. Conclusion. Inhibition of motility and invasion by PFEs, coincident with suppressed RhoC and RhoA protein expression, suggests a role for these defined extracts in lowering the metastatic potential of aggressive breast cancer species.

Inhibition of Viral Carcinogenesis by Phyllanthus amarus

Harikumar, K. B., Kuttan, G., Kuttan, R. — Thu, 08 Oct 2009 04:26:33 PDT

Friend murine leukemia virus (FMuLv) is an acutely oncogenic retrovirus, and its infection leads to erythroblastosis and leukemia in mice. This infection model is used in the search for new antiviral agents. In the present study, the authors have evaluated the potential of an extract of Phyllanthus amarus against FMuLv-induced erythroleukemia in BALB/c mice. Injection of newborn mice with FMuLv resulted in leukemia and animals died due to splenomegaly. Oral administration of P.amarus was found to enhance the life span of leukemia-harboring animals and decrease the incidence of anemia. The authors also performed a series of hematological, biochemical, histopathological, and gene expression analyses to evaluate the effect of P.amarus administration on erythroleukemia initiation and progression. The data obtained indicate that P.amarus administration could significantly decrease the progression of erythroleukemia. Treatment with P.amarus induced the expression of p53 and p45NFE2 and decreased the expression of Bcl-2 in the spleen of infected mice. Histopathological evaluations of the spleen demonstrated that administration of P.amarus decreased the infiltration of leukemic cells into the sinusoidal space when compared with the vehicle treated group. P.amarus is known to inhibit chemically induced neoplasm in different rodent models.The current results indicate that P.amarus has the ability to suppress virally induced cancers as well.

Podophyllum hexandrum Fraction (REC-2006) Shows Higher Radioprotective Efficacy in the p53-Carrying Hepatoma Cell Line: A Role of Cell Cycle Regulatory Proteins

Thu, 08 Oct 2009 04:26:33 PDT

The present study was carried out to evaluate the radioprotective efficacy of Podophyllum hexandrum fraction (REC-2006) in hepatoma cell lines having different p53 statuses. Higher radioresistance was observed in the HepG2 (p53⁺⁺) cell line in comparison to the Hep3B (p53^--) cell line, indicating a plausible role of p53 in radioresistance. REC-2006 exhibited nearly twice the survival in p53-expressing HepG2 cells compared with p53-negative Hep3B cells. REC-2006 treatment alone induced p53 expression as compared with untreated controls. However, REC-2006 reduced p53 expression when treated 2 hours before irradiation as compared with the irradiated HepG2 controls, indicating that REC-2006 modulates the expression of p53 to mitigate its apoptotic effect. Induction of p21 in the REC-2006 + radiation treatment group downregulated the expression of cyclin E and CDK2, leading to a delay in the G1 phase of HepG2 cells, which provided time for DNA repair or related processes. However, no significant difference in CDC2 expression in both cell lines suggested that G2 phase arrest might not be the only responsible factor for REC-2006-mediated radioprotection. Significant induction of PCNA and GADD45 expression in HepG2 cells suggested that REC-2006 increased the percentage survival of HepG2 cells by increasing the span of time as well as efficacy for repair processes. In conclusion, REC-2006 modulated the expression of p53 and thereby promoted cell cycle arrest in the G1 phase, encouraging cell proliferation and DNA repair and thus providing significantly higher protection against acute -radiation in the HepG2 cell line.

Anticancer Activity of an Indian Medicinal Plant, Alstonia scholaris, on Skin Carcinogenesis in Mice

Jahan, S., Chaudhary, R., Goyal, P. K. — Thu, 08 Oct 2009 04:26:33 PDT

Alstonia scholaris, commonly known as sapthaparna, has been used for centuries in Ayurvedic medicine for treatment of various disorders. The objective of this study was to investigate the possible chemopreventive and anti-oxidative properties of this medicinal plant on two-stage process of skin carcinogenesis induced by a single application of 7, 12-dimethyabenz(a)anthrecene (100 lg/100 ll acetone), and two weeks later, promoted by repeated application of croton oil (1% in acetone/thrice a week) till the end of the experiment (16 weeks) in Swiss albino mice.The tumor incidence, tumor yield, tumor burden and cumulative number of papillomas were found to be higher in the carcinogen treated control (without ASE treatment) as compared to experimental animals (ASE treated). Furthermore, a significant increase in reduced glutathione, superoxide dismutase and catalase but decrease in lipid peroxidation was measured in ASE administered experimental groups than the carcinogen treated control. The present study demonstrates the chemopreventive potential of Alstonia scholaris bark extract in DMBA-induced skin tumorigenesis in Swiss albino mice.

Gamma Knife--Treated Hepatoma: Case of Obstructive Jaundice and Management

Wang, M.-Q., Zou, Q., He, Q., Guan, Y.-S. — Thu, 08 Oct 2009 04:26:33 PDT

Gamma knife therapy is becoming more frequently applied in solid tumor treatment. This article reports a unique case of severe obstructive jaundice arising as a complication of treatment of hepatoma at the hepatic hilum using a gamma knife.While planning an intervention, some images seem to promise success but actually lead to failure. Radiation damage to specific organs is difficult to predict because of several variables. Radiation-induced fibrosis and necrosis are the most common long-term adverse effects of radiotherapy; they are usually considered irreversible and result in induration and firmness of the tissue.To minimize radiation fibrosis, accurate patient positioning and tumor relocalization are essential for gamma knife use in the liver and other extracranial sites. Even when practiced frequently, any intervention must be delivered with caution if the liver has been treated with radiation. Otherwise, even with much experience, the unwary doctor can be trapped by deceptive images.

Sonodynamic and Photodynamic Therapy in Advanced Breast Carcinoma: A Report of 3 Cases

Wang, X., Zhang, W., Xu, Z., Luo, Y., Mitchell, D., Moss, R. W. — Thu, 08 Oct 2009 04:26:33 PDT

Photodynamic therapy (PDT) is an established therapeutic method, first approved by the FDA for certain kinds of cancer in 1998. There are also increasing data to show that a related procedure, sonodynamic therapy (SDT), is a promising new modality for cancer treatment. Here, the authors report clinical results in 3 advanced refractory breast cancer patients who were treated using a combination of sonodynamic and photodynamic therapy (SPDT), along with conventional therapies. All 3 patients had pathologically proven metastatic breast carcinoma. These widely disseminated carcinomas had ultimately failed to respond to conventional therapy. A new sensitizing agent, Sonoflora 1^TM (SF1) was administered sublingually; then, after a 24-hour delay, patients were treated with a combination of light and ultrasound. All patients had significant partial or complete responses. SPDT is a promising new therapeutic combination for the treatment of breast cancer.

In This Issue

Block, K. I. — Thu, 13 Aug 2009 04:44:12 PDT

Letter to the Editor

Zia, F. Z., White, J. D. — Thu, 13 Aug 2009 04:44:12 PDT

Aging and Cancer: Converging Routes to Disease Prevention

Chobotova, K. — Thu, 13 Aug 2009 04:44:12 PDT

An integrative approach to the combined challenges of aging, cancer and stress is a necessary part of a global vision of wellness. Recent research into the mechanisms of aging, cancer and stress has established the biological links between these processes. Understanding these links is an important stepping-stone for developing approaches and therapies that ensure wellness throughout all stages of aging. This paper will consider the most recent developments in research into the molecular mechanisms common to aging and cancer and will discuss the effectiveness of natural approaches for preventing disease. Metabolic regulators as well as nutrient and energy sensors are involved in the processes of aging and cancer, and these are open to external manipulation and control. It is now becoming possible to demonstrate how nutrition, physical activity and stress control can lead to disease-free aging.

Feasibility Trial of Electroacupuncture for Aromatase Inhibitor--Related Arthralgia in Breast Cancer Survivors

Thu, 13 Aug 2009 04:44:12 PDT

Background. Arthralgia affects postmenopausal women receiving aromatase inhibitors (AIs) for breast cancer. Given the existing evidence for electroacupuncture (EA) for treatment of osteoarthritis in the general population, this study aims to establish the feasibility of studying EA for treating AI-related arthralgia. Patients and Methods. Postmenopausal women with stage I-III breast cancer who reported AI-related arthral gia were enrolled in a single-arm feasibility trial. EA was provided twice a week for 2 weeks followed by 6 weekly treatments. The protocol was based on Chinese medicine diagnosis of "Bi" syndrome with electrostimulation of needles around the painful joint(s). Pain severity of the modified Brief Pain Inventory was used as the primary outcome. Joint stiffness, joint interference, and Patient Global Impression of Change (PGIC) were secondary outcomes. Paired t tests were used for analysis. Results. Twelve women were enrolled and all provided data for analysis. From baseline to the end of intervention, patients reported reduction in pain severity (from 5.3 to 1.9), stiffness (from 6.9 to 2.4), and joint symptom interference (from 4.7 to 0.8), all P < .001; 11/12 considered joint symptoms "very much better" based on the PGIC. Subjects also reported significant decrease in fatigue (from 4.4 to 1.9, P = .005) and anxiety (from 7.1 to 4.8, P = .01). No infection or development or worsening of lymphedema was observed. Conclusion. Preliminary data establish the feasibility of recruitment and acceptance as well as promising preliminary safety and effectiveness. A randomized controlled trial is warranted to establish the efficacy of EA for AI-related arthralgia in breast cancer survivors.

The Effects of an Exercise Program in Leukemia Patients

Battaglini, C. L., Hackney, A.C., Garcia, R., Groff, D., Evans, E., Shea, T. — Thu, 13 Aug 2009 04:44:12 PDT

Purpose. To examine the feasibility of administering an in-hospital exercise program to acute leukemia patients undergoing chemotherapy. A secondary purpose explored the impact of exercise on selected physiological, psychological, and inflammatory markers. Methods. Ten patients, aged 18 to 50 years, diagnosed with acute leukemia or newly relapsed were assessed for body weight, height, body composition (skinfolds), cardiorespiratory endurance (total minutes on bicycle ergometer at 60% heart rate reserve), dynamic muscular endurance (Rocky Mountain Cancer Rehabilitation Institute protocol), fatigue (Revised Piper Fatigue Scale), depression (Center for Epidemiologic Studies Depression scale, National Institute of Mental Health questionnaire), and quality of life (Functional Assessment of Cancer Therapy—General) at baseline (within 3 days of diagnosis) and at the end of induction phase of treatment. Blood draws were taken at baseline, midpoint, and at the end of induction for analyses of inflammatory markers (Linco Luminex assay). Combined aerobic and strength training exercises were administered 3 times per week, twice daily, for 30 minutes. Paired-samples t-tests were used for the analyses of physiological and psychological parameters. One-way repeated measures analysis of variance was used for the analyses of inflammatory markers. Results. Significant improvements in cardiorespiratory endurance (P = .009, baseline 8.9 ± 8.8 minutes, postexercise intervention 17 ± 14.3 minutes) with significant reductions in total fatigue scores (P = .009, baseline 4.6 ± 1.7, postexercise intervention 1.8 ± 1.6) and depression scores (P = .023, baseline 19 ± 11.5, postexercise intervention 12 ± 8.2) were observed. Marginally significant decrease in interleukin-6 (IL-6; P = .059) with no significant changes in IL-10 (P = .223) or interferon- (P = .882) were observed. Conclusion. Administration of exercise to acute leukemia patients undergoing treatment is feasible. The exercise protocol used increased cardiovascular endurance, reduced fatigue and depression scores, and maintained quality of life. Although no significant change in inflammation was observed, a trend demonstrating a reduction in IL-6 and an increase in IL-10 warrants further investigation.

Aerobic Exercise Intensity in Breast Cancer Patients: A Preliminary Investigation

Evans, E. S., Battaglini, C. L., Groff, D. G., Hackney, A.C. — Thu, 13 Aug 2009 04:44:12 PDT

Purpose: This study compared the heart rate (HR), rate of perceived exertion (RPE), and blood lactate (BL) responses to aerobic exercise between posttreated breast cancer patients and apparently healthy, age-matched controls. Methods: Seven patients and 7 control subjects underwent a submaximal treadmill test for the estimation of Vo_2max. Exercise intensities of 40%, 60%, and 70% of Vo_2max were calculated from the treadmill test and randomly examined between groups during three 9-minute exercise bouts on 3 different days. Independent samples t tests were used to examine the HR, RPE, and BL responses at each intensity between groups. Results: No significant differences were observed between the control and patient groups for HR, RPE, and BL at 40% (101 ± 9 vs 101 ± 11 bpm, P = .979; 8 ± 1 vs 9 ± 3, P = .237; and 1.11 ± 0.73 vs 1.26 ± 0.64 mmol/L, P = .188, respectively) and 60% (127 ± 17 vs 117 ± 13 bpm, P = .523; 12 ± 2 vs 11 ± 3, P = .267, and 3.83 ± 2.48 vs 2.23 ± 1.65 mmol/L, P = .237, respectively) of Vo_2max . At 70% of Vo_2max, no significant differences were found for HR (151 ± 27 vs 135 ± 13 bpm, P = .704) and RPE (14 ± 1 vs 13 ± 3, P = .181), but lower BL responses were observed in the patient group (7.70 ± 1.62 vs 3.29 ± 1.08 mmol/L, P < .0005). Conclusions: The results suggest similar HR, RPE, and BL responses between patients and control subjects at 40%, 60%, and 70% of Vo_2max , except for BL at 70% of Vo_2max. The lower BL response in the patient group at 70% of Vo_2max was somewhat unexpected. Further research is needed to confirm or refute the results of this study to allow for a clearer understanding of the physiological responses of breast cancer patients to aerobic exercise at moderate or higher intensities so that safer aerobic exercise prescriptions can be developed for this population.

Impact of Standardized Rhus verniciflua Stokes Extract as Complementary Therapy on Metastatic Colorectal Cancer: A Korean Single-Center Experience

Lee, S.-h., Choi, W.-c., Yoon, S.-w. — Thu, 13 Aug 2009 04:44:12 PDT

Background. To investigate the clinical feasibility of the standardized Rhus verniciflua Stokes (RVS) extract for the metastatic colorectal cancer (mCRC), experimentally proven to have anticancer activities. Patients and Methods. From July 2006 to November 2007, patients with conventional chemotherapy refractory mCRC were checked. After fulfilling inclusion/exclusion criteria, 36 patients were eligible for the final analysis. Overall survival and adverse events of patients treated with RVS in the aftercare period were determined. Results. On October 21, 2008, a total of 26 patients died while the remaining 10 patients were alive with evidence of disease. The median RVS administration period was 2.7 months (95% confidence interval, 1.9-3.5). The median overall survival for the entire population was 10.9 months (95% confidence interval, 5.6-16.1) and 1-year survival rate was 44.4%, which is compatible with external controls. By survival analysis using Cox proportional hazards model, the performance status and the prior chemotherapy regimen number significantly affected overall survival. Adverse reactions to the RVS treatment were mostly mild and self-limiting. Conclusion. Complementary treatment with the standardized RVS extract might be beneficial for patients with mCRC, since it positively affected overall survival without significant side effects. This study suggests that RVS could be a natural anticancer agent candidate for the treatment of colorectal adenocarcinoma.

What Is an Exceptional Cancer Trajectory?: Multiple Stakeholder Perspectives on Cancer Trajectories in Relation to Complementary and Alternative Medicine Use

Hok, J., Forss, A., Falkenberg, T., Tishelman, C. — Thu, 13 Aug 2009 04:44:12 PDT

Background: Although links between exceptional cancer trajectories (ECTs) and complementary and alternative medicines (CAMs) have been suggested, most research on ECT uses predefined criteria for ECTs without necessarily including CAM use. Little knowledge can be found about subjective perspectives of ECTs in relation to CAM. Objectives: This Swedish study explores how patients, significant others, and CAM and biomedical health care (BHC) providers reason about ECT, including the role of CAM. Methods: Using a case study approach, open interviews were conducted with multiple stakeholders about cancer trajectories reported as exceptional. Results: In-depth analysis of 5 cases indicated that although all stakeholders agreed that the reported cases were positive, in no case was the same trajectory considered exceptional by all stakeholders. Different stakeholders shared neither conceptualizations of what constituted an ECT nor attributions for positive trajectories. Patients, significant others, and CAM providers emphasized unexpectedly long survival and well-being in ECTs, whereas BHC providers only referred to survival. CAM and BHC providers normalized reported trajectories, although the forms for this differed between provider groups. Concluding discussion: Stakeholders' accounts are discussed relative to different health care domains, legitimization processes, and legal constraints, which have led to the lack of a public sphere for CAM use in cancer.

An Alternative Treatment for Cervical Intraepithelial Neoplasia II, III

Swanick, S., Windstar-Hamlin, K., Zwickey, H. — Thu, 13 Aug 2009 04:44:12 PDT

Background. This report describes a case of a woman with progressive and recurrent cervical dysplasia 4 years after cervical conization for severe dysplasia. Patient and methods. A 20-year-old female was referred for colposcopy and biopsy following results of moderate to severe atypia of cervical cells on her Papanicolaou (Pap) test. Her colposcopy was satisfactory and her biopsy revealed cervical intraepithelial neoplasia (CIN) II, III. She refused the conventional recommendation of loop electrosurgical excision procedure (LEEP) and, as an alternative, elected to receive escharotic treatment at a frequency of 2 treatments per week for 5 weeks. In addition to the escharotic treatment she followed an oral vitamin and botanical protocol. She was followed for 5 years. Results. The patient's 4-month and 10-month follow-up Pap smears revealed negative cervical cytology for intraepithelial lesion or malignancy. Her 10-month colposcopy was satisfactory and no lesions were noted on the colposcopic exam. Liquid based Pap results continued to remain normal for 5 years after the initiation of treatment. Discussion. Escharotic treatment of high-grade cervical neoplasias with satisfactory colposcopy holds promise as an effective and low-risk alternative therapy to LEEP and other excisional procedures.

Marked Inhibition of Growth and Invasive Parameters of Head and Neck Squamous Carcinoma FaDu by a Nutrient Mixture

Roomi, M.W., Roomi, N.W., Kalinovsky, T., Rath, M., Niedzwiecki, A. — Thu, 13 Aug 2009 04:44:12 PDT

Head and neck squamous cell carcinomas (HNSCCs) are known for their aggressive growth and propensity to metastasize. The authors investigated the effect of a novel nutrient mixture (NM) containing ascorbic acid, lysine, proline, and green tea extract on human HNSCC cell line FaDu in vivo and in vitro. Athymic male nude mice (n = 12) were inoculated with 3 x 10⁶ FaDu cells subcutaneously and randomly divided into 2 groups: group A was fed a regular diet and group B a regular diet supplemented with 0.5% NM. Four weeks later, the mice were sacrificed and their tumors were excised, weighted, and processed for histology. In vitro, FaDu cells were cultured in Dulbecco's modified Eagle's medium and exposed to NM at 0 to 1000 µg/mL in triplicate. Cell proliferation was assessed by MTT assay, matrix metalloproteinase (MMP) secretion by gelatinase zymography, invasion through Matrigel, apoptosis by live-green caspases, and cell morphology by hematoxylin—eosin staining. NM inhibited the growth of tumors by 55% (P = .0002) and exhibited dose-dependent toxicity on FaDu cells in vitro, with 53% (P = .0003) at 1000 µg/mL NM. Zymography revealed MMP-2 and phorbol 12-myristate 13-acetate—induced MMP-9 secretion. NM inhibited secretion of both MMPs in a dose-dependent manner, with virtual total inhibition at 1000 µg/mL. NM significantly inhibited FaDu invasion through Matrigel with total block at 1000 µg/mL. NM induced dose-dependent apoptosis. In conclusion, NM has therapeutic potential in the treatment of HNSCC by significantly suppressing tumor growth and significantly inhibiting MMP secretion and invasion of HNSCC cells in vitro.

Potency of Andrographolide as an Antitumor Compound in BHC-Induced Liver Damage

Trivedi, N. P., Rawal, U. M., Patel, B. P. — Thu, 13 Aug 2009 04:44:12 PDT

Relevance. The present investigation relates to the influence of andrographolide, an active compound of Andrographis paniculata Nees. It reverses an experimental liver carcinogenic condition of mice to normal and might be a potential therapeutic/preventive agent for human liver cancer. Objective. A. paniculata (Kalmegh) is extensively used in the Indian traditional system of medicine as a hepatoprotective and hepatostimulative agent and has been reported to have protective effect against different hepatotoxins. Materials and methods. Histomorphological, ultrastructural, and biochemical studies were performed for the effect of the andrographolide on control mice, mice treated with hexachlorocyclohexane (BHC) only and BHC + andrographolide. Enzymes for liver function tests were analyzed by spectrophotometric method. Results. The BHC experimental model forms an irreversible liver tumor in male mice. The histological and ultrastructural changes observed in andrographolide supplementation emphasize the recovery of the damaged liver. This recovery was also reflected in the neoplastic nodule formation. The activity of phosphorylase and glucose-6-phosphatase in the liver of the andrographolide-supplemented group suggests improved glycogenolysis in liver. Serum glutamate pyruvate transaminase, serum glutamate oxalate transaminase, alkaline phosphatase, acid phosphatase, and -glutamyl transpeptidase showed a significant decrease in andrographolide-supplemented animals as compared with BHC-treated animals, suggesting regenerative effects elicited by andrographolide. Conclusion. The study indicates that the regenerative capability elicited by andrographolide is possibly due to its ability to reactivate liver function enzymes that catalyze the reaction of several biochemical and synthetic processes and that it may be useful for severe liver damage conditions.

Phyllanthus amarus Inhibits Cell Growth and Induces Apoptosis in Dalton's Lymphoma Ascites Cells Through Activation of Caspase-3 and Downregulation of Bcl-2

Harikumar, K. B., Kuttan, G., Kuttan, R. — Thu, 13 Aug 2009 04:44:12 PDT

The authors found in an earlier study that Phyllanthus amarus extract could significantly inhibit the solid and ascites tumor development in mice induced by Dalton's lymphoma ascites (DLA) cells. In the present study, the apoptotic effects of P.amarus against DLA cells in culture was evaluated. P.amarus produced significant reduction in cell viability as determined by the MTT assay. It also induces the formation of apoptotic bodies with characteristic features like plasma membrane invagination, elongation, fragmentation, and chromatin condensation. P.amarus at concentrations of 100 and 200 µg/mL is shown to induce DNA fragmentation. Gene expression analysis reveals that P.amarus induces the expression of caspase-3 and inhibits the expression of Bcl-2, which is an antiapoptotic protein. So the present study provides some insights into the possible mechanism by which P.amarus brings about apoptosis and growth inhibition in DLA cells.

Errata

Thu, 13 Aug 2009 04:44:12 PDT

In the article "Effect of Withaferin A on the Development and Decay of Thermotolerance in B16F1 Melanoma: A Preliminary Study" by Kalthur et al, published in the March 2009 issue (Integrative Cancer Therapies, 8(1):93-97; first published on February 3, 2009, doi: 10.1177/1534735408330715), data in the abstract appeared incorrectly. The abstract below has been reprinted with the correct data.

Errata

Thu, 13 Aug 2009 04:44:12 PDT

In the article "Effects of a Yoga Program on Cortisol Rhythm and Mood States in Early Breast Cancer Patients Undergoing Adjuvant Radiotherapy: A Randomized Controlled Trial", published in the March 2009 issue (Integrative Cancer Therapies,8(1):37-46; first published on February 3, 2009, doi: 10.1177/1534735409331456), the name of the first author was incorrectly published as Rao M. Raghavendra. The first author of the article is H.S. Vadiraja and Rao M. Raghavendra is the corresponding author for the article.

Errata

Thu, 13 Aug 2009 04:44:12 PDT

In the article "Inhibitive Effect of Artemether on Tumor Growth and Angiogenesis in the Rat C6 Orthotopic Brain Gliomas Model", Zhi-ping Wu et al., published in the March 2009 issue (Integrative Cancer Therapies, 8(1):88-92; first published on January 27, 2009, doi: 10.1177/1534735408330714), the name of the corresponding author was incorrectly published as Zhi-ping Wu. The corresponding author for the article is Qi-shun Zhu, 2#Cuifu Northern Road, Kunming 650091, China; e-mail: qshzhu@ynu.edu.cn. This has been published for the convenience of the reader and the authors.

In This Issue

Block, K. I. — Tue, 17 Feb 2009 05:29:55 PST

Antioxidants: SELECTed out?

Block, K. I. — Tue, 17 Feb 2009 05:29:55 PST

A Comparative Review of Thermography as a Breast Cancer Screening Technique

Kennedy, D. A., Lee, T., Seely, D. — Tue, 17 Feb 2009 05:29:56 PST

Breast cancer is the most frequently diagnosed cancer of women in North America. Despite advances in treatment that have reduced mortality, breast cancer remains the second leading cause of cancer induced death. Several well established tools are used to screen for breast cancer including clinical breast exams, mammograms, and ultrasound. Thermography was first introduced as a screening tool in 1956 and was initially well accepted. However, after a 1977 study found thermography to lag behind other screening tools, the medical community lost interest in this diagnostic approach. This review discusses each screening tool with a focus brought to thermography. No single tool provides excellent predictability; however, a combination that incorporates thermography may boost both sensitivity and specificity. In light of technological advances and maturation of the thermographic industry, additional research is required to confirm the potential of this technology to provide an effective non-invasive, low risk adjunctive tool for the early detection of breast cancer.

Trastuzumab and Doxorubicin-Related Cardiotoxicity and the Cardioprotective Role of Exercise

Wonders, K. Y., Reigle, B. S. — Tue, 17 Feb 2009 05:29:56 PST

Women diagnosed with breast cancer typically undergo a multimodal approach to treating their disease. The treatments used often result in sequelae such as fatigue, hair loss, nausea and vomiting, and functional impairment. Many of these sequelae can be controlled or eliminated with pharmacological, physical, or social interventions. However, 2 effective cytotoxic agents, doxorubicin and trastuzumab, are associated with a potentially life-threatening sequela, cardiotoxicity. Currently, these agents are dosage and duration limited to circumvent cardiac damage. Exercise prior to and during the administration of these agents is emerging as a possible cardioprotective intervention based on the findings of animal model studies. Incorporating exercise into the breast cancer treatment trajectory may eliminate the dosage and duration restrictions of these antineoplastic agents and ultimately affect survival and quality of life. The authors present the pharmacological mechanism for each agent and the exciting results of animal model studies that lay the groundwork for future clinical trials.

Nutrition and the Prevention and Treatment of Cancer: Association of Cytochrome P450 CYP1B1 With the Role of Fruit and Fruit Extracts

Ware, W. R. — Tue, 17 Feb 2009 05:29:56 PST

Recommendations for a healthy or prudent diet include a large number of daily servings of fruits and vegetables, and these 2 classes of food are widely believed to assist in cancer prevention. One potential mechanism that is rarely mentioned in nutritional studies involves the cytochrome P450 enzyme CYP1B1, which appears to have the unique properties of being a universal cancer marker overexpressed in cancer cells and having the capability of converting various phytochemicals and synthetic chemicals into substances cytotoxic to these cells. Although these particular features of CYP1B1 have not gone unnoticed, there has been relatively little research aimed at exploiting them. Furthermore, therapeutic and preventive strategies currently being considered based on vaccines against the enzyme or inhibition without the generation of cytotoxins can be questioned because they do not take advantage of the unique properties of this enzyme. In addition, a few relevant case histories have been published that use specially designed fruit extracts containing substrates with demonstrated cytotoxic metabolic products, and these reports provide an initial confirmation of the potential of exploiting the unusual properties of this enzyme for cancer therapy.

Identification and Exploration of Herb-Drug Combinations Used By Cancer Patients

Engdal, S., Klepp, O., Nilsen, O. G. — Tue, 17 Feb 2009 05:29:56 PST

Introduction: This survey aims to identify herb-chemotherapeutic drug combinations in a defined group of cancer patients and to explore possible clinical consequences of these combinations. Methods: Herb-chemotherapeutic drug combinations were identified among adult cancer patients, and clinical consequences of the combinations were explored by literature searches in medical databases on possible mutual effects on similar cytochrome P-450 metabolising enzymes (CYPs) and/or the P-glycoprotein (P-gp) transporter. Results: Among 42 cancer patients using herbal remedies concurrently with chemotherapy, 136 two-agent herb-drug combinations were registered and 47 different potential herb-drug interactions were identified on the level of CYP metabolism and P-gp transport in vitro. Garlic, ginger, green tea and noni juice were the herbal remedies most frequently used in such combinations. For 48 % of the herbal remedies identified no literature data exist on their interaction potentials. Clinical studies were available for four herbal remedies only. Minor clinical potential for CYP interactions in humans was indicated for green tea and Echinacea. P-gp interactions were only investigated for garlic, which showed a significant interaction potential both in vivo and in vitro. Conclusion: The large number of in vitro potential herb-drug interactions identified urge for more clinical pharmacokinetic interaction studies in humans.

Effects of a Yoga Program on Cortisol Rhythm and Mood States in Early Breast Cancer Patients Undergoing Adjuvant Radiotherapy: A Randomized Controlled Trial

Tue, 17 Feb 2009 05:29:56 PST

Objectives. This study compares the effects of an integrated yoga program with brief supportive therapy in breast cancer outpatients undergoing adjuvant radiotherapy at a cancer center. Methods. Eighty-eight stage II and III breast cancer outpatients are randomly assigned to receive yoga (n = 44) or brief supportive therapy (n = 44) prior to radiotherapy treatment. Assessments include diurnal salivary cortisol levels 3 days before and after radiotherapy and self-ratings of anxiety, depression, and stress collected before and after 6 weeks of radiotherapy. Results. Analysis of covariance reveals significant decreases in anxiety (P < .001), depression (P = .002), perceived stress (P < .001), 6 a.m. salivary cortisol (P = .009), and pooled mean cortisol (P = .03) in the yoga group compared with controls. There is a significant positive correlation between morning salivary cortisol level and anxiety and depression. Conclusion. Yoga might have a role in managing self-reported psychological distress and modulating circadian patterns of stress hormones in early breast cancer patients undergoing adjuvant radiotherapy.

Evaluation of the Effects of a Psychosocial Intervention on Mood, Coping, and Quality Of Life in Cancer Patients

Reavley, N., Pallant, J. F., Sali, A. — Tue, 17 Feb 2009 05:29:56 PST

It was hypothesized that participation in a psychosocial intervention incorporating meditation, social support, positive thinking, and a low-fat, vegetarian diet would have beneficial effects on mood, coping, and quality of life (QOL) in cancer patients. This article describes the sociodemographic, medical, and psychological characteristics of participants in a psychosocial intervention designed for cancer patients. It also describes program impact in terms of Profile of Mood States, Mini-Mental Adjustment to Cancer, and Functional Assessment of Chronic Illness Therapy. Compliance with program recommendations for 3 months and effects on adjustment were also explored. Improvements in all measures were found at program completion, with spiritual well-being particularly linked to improvement in QOL. The results suggest that the program has significant beneficial effects on adjustment but that these may not be fully maintained at follow-up, possibly because of difficulty in incorporating program recommendations into everyday life, increasing disease severity, and lack of accountability.

Patients of an Interdisciplinary Cancer Treatment Center: Use of, Knowledge About, and Demand for CAM Treatment Options

Eustachi, A., Pajtler, H., Linde, K., Melchart, D., Weidenhammer, W. — Tue, 17 Feb 2009 05:29:56 PST

Objective: to assess the use of, knowledge about, and the demand for information concerning complementary and alternative medicine (CAM) in cancer patients. Methods: A cross-sectional survey was performed on consecutive patients visiting the outpatient tumor treatment center of a university hospital at Munich, Germany. The authors used a questionnaire with questions on sociodemographics, tumor diagnosis and treatment, current symptoms, previous use of CAM, and expectations and attitudes with respect to CAM. Results: 52% used at least 1 CAM method, 24% did not use CAM but asked for consultation, and 24% neither used CAM nor were interested; 59% rated CAM treatment as personally important; 76% and 34% described themselves as well informed about conventional treatment and CAM, respectively. Current CAM use was associated with higher degrees of information and subjective importance, and not suffering from lymphatic cancer and metastases. Conclusions: CAM is a relevant topic for the care of cancer patients.

Patients' Interactions With Physicians and Complementary and Alternative Medicine Practitioners: Older Women With Breast Cancer and Self-Managed Health Care

Adler, S. R., Wrubel, J., Hughes, E., Beinfield, H. — Tue, 17 Feb 2009 05:29:56 PST

Older patients are more likely than ever to be under the care of both physicians and complementary and alternative medicine (CAM) practitioners, yet there is little research on older patients' experience of these different relationships. This article addresses older breast cancer patients' seeking of concurrent care and examines patients' understandings of interactions with physicians and CAM practitioners. This is a qualitative study of a random, population-based sample of 44 older women with breast cancer who are simultaneously under the care of at least 1 physician and 1 CAM practitioner.

Anticancer Effects of HESA-A in Patients With Metastatic Colon Cancer

Ahmadi, A., Mohagheghi, M., Karimi, M., Seyed Ali Golestanha, , Naseri, M. — Tue, 17 Feb 2009 05:29:56 PST

Background: HESA-A is a natural biological compound of herbal—marine origin. The aim of this study was to investigate the therapeutic effects of HESA-A in patients with metastatic colon cancer. Methods: Fifty consecutive patients with end-stage colon cancer and liver metastasis at the Cancer Research Center of Tehran University of Medical Sciences were studied. Patients received HESA-A 50 mg/kg/d orally in 2 to 3 divided doses for 6 months. The patients were assessed at the start and end of the 1st, 2nd, 4th, 8th, 12th, 16th, 20th, and 26th weeks of the study. The Karnofsky Performance Scale questionnaire was completed for each patient. Results: The mean Karnofsky performance score increased from 33.6 ± 9.8 to 63.3 ± 11 after 10 weeks of study. No significant hepatic or hematological adverse effects were seen during the study. Conclusion: It seems that HESA-A is an effective and safe anticancer drug, which can be used in selected patients.

Antiangiogenic and Proapoptotic Activities of Allyl Isothiocyanate Inhibit Ascites Tumor Growth in Vivo

Kumar, A., D'Souza, S. S., Tickoo, S., Salimath, B. P., Singh, H.B. — Tue, 17 Feb 2009 05:29:56 PST

The authors investigate the antiangiogenic and proapoptotic effects of mustard essential oil containing allyl isothiocyanate (AITC) and explore its mechanism of action on Ehrlich ascites tumor (EAT) cells. Swiss albino mice transplanted with EAT cells were used to study the effect of AITC. AITC was effective at a concentration of 10 µm as demonstrated by the inhibition of proliferation of EAT cells when compared with the normal HEK293 cells. It significantly reduced ascites secretion and tumor cell proliferation by about 80% and inhibited vascular endothelial growth factor expression in tumor-bearing mice in vivo. It also reduced vessel sprouting and exhibited potent antiangiogenic activity in the chorioallantoic membrane and cornea of the rat. AITC arrested the growth of EAT cells by inducing apoptosis and effectively arrested cell cycle progression at the G1 phase. The results clearly suggest that AITC inhibits tumor growth by both antiangiogenic and proapoptotic mechanisms.

Inhibitive Effect of Artemether on Tumor Growth and Angiogenesis in the Rat C6 Orthotopic Brain Gliomas Model

Tue, 17 Feb 2009 05:29:56 PST

To explore the inhibitive effect of artemether on glioma growth and angiogenesis in brain tumor bearing SD rat. MTT assay was used to evaluate the inhibitory effect of artemether treatment on C6 glioma cells. Forty SD rats which were subcutaneous planted with SD rat C6 glioma cell to establish SD rat orthotopic glioma model were divided resourcefully into 5 groups. each group was 8 rats. Length-path (a mm) and short-path (b mm) of tumor each rat was measured. Tumor volume was calculated using the following formula: V (mm³) = a²b_/6. Microvessel density (MVD) in different therapy groups was significantly lower than that in normal saline control group and brain glioma volume in different therapy groups was significantly smaller than that in normal saline control group. There were remarkably inhibitory effects of artmeter on brain glioma growth and angiogenesis in SD rats and the mechanism that artemether inhibited brain glioma growth might be penetrating the blood-brain barrier and inhibiting angiogenesis.

Effect of Withaferin A on the Development and Decay of Thermotolerance in B16F1 Melanoma: A Preliminary Study

Kalthur, G., Mutalik, S., Pathirissery, U. D. — Tue, 17 Feb 2009 05:29:56 PST

Protein synthesis inhibitors can suppress the development of thermotolerance in tumor tissues on repeated heating. Withaferin A (WA), isolated from Withania somnifera has cytotoxic and inhibitory action on protein synthesis. In the present investigation, effect of WA on development and decay of thermotolerance in B16F1 melanoma was studied in C57BL mice. Tumors of 10010 mm3 size were subjected to repeated hyperthermia (HT) at 43°C for 30 minutes. WA was injected after first hyperthermia treatment. The tumor response was assessed by calculating the tumor growth delay (GD). The GD increased with increase in time gap between two hyperthermia treatments and was significantly higher (p < 0.05 to p < 0.001) in WA treated groups at all the respective time gaps (except at 0h and 120h) compared to hyperthermia alone group. WA increases the tumor response during repeated hyperthermia by reducing the magnitude of thermotolerance developed and by decreasing the recovery time from thermotolerance.

Protective Effect of an Extract of Emblica officinalis Against Radiation-Induced Damage in Mice

Jindal, A., Soyal, D., Sharma, A., Goyal, P.K. — Tue, 17 Feb 2009 05:29:56 PST

The radioprotective effect of Emblica officinalis extract (EOE) was studied in mice. Swiss albino mice were exposed to rays (5 Gy) in the absence (control) or presence (experimental) of EOE, orally 100 mg/kg body weight, once daily for 7 consecutive days. A specimen of small intestine (jejunum) was removed from the mice and studied at different autopsy intervals from 12 hours to 30 days. In control animals, crypt cell population, mitotic figures, and villus length were markedly reduced on day 1; these later started to increase progressively but did not attain the normal level even at the last autopsy interval. The animals receiving EOE prior to irradiation had a higher number of crypt cells and mitotic figures when compared with non-drug-treated control at all the autopsy intervals. Irradiation of animals resulted in a dose-dependent elevation in lipid peroxidation and a reduction in glutathione as well as catalase concentration in the intestine at 1 hour post-irradiation. In contrast, EOE treatment before irradiation caused a significant depletion in lipid peroxidation and elevation in glutathione and catalase levels.

Enzymes and Cancer: A Look Toward the Past as We Move Forward

Block, K. I. — Tue, 30 Dec 2008 03:59:31 PST

Introduction to the John Beard Special Issue

Moss, R. W. — Tue, 30 Dec 2008 03:59:31 PST

The Life and Times of John Beard, DSc (1858-1924)

Moss, R. W. — Tue, 30 Dec 2008 03:59:31 PST

The British developmental biologist John Beard, DSc (1858-1924) is little remembered today. Yet, he made outstanding contributions to the life sciences. Beard deserves to be included among the leading biologists of the late 19th and early 20th century. He has been hailed as a forerunner of the present-day theory of the cancer stem cell (CSC). He was the first to point to the parallels between cancer and the trophoblastic cells that envelop and nourish the embryo, characterizing cancer as "irresponsible trophoblast." He pointed out that the initiation of fetal pancreatic function coincided with a reduction in the invasiveness of trophoblast, which otherwise might progress to clinical cancer (ie, choriocarcinoma). Based on the above propositions, he recommended the therapeutic use of pancreatic enzymes in treating cancer and other diseases. This therapy created a worldwide controversy, and although rejected in his day, persists in the world of complementary and alternative medicine (CAM) today.

John Beard Timeline

Moss, R. W. — Tue, 30 Dec 2008 03:59:31 PST

Enzymes, Trophoblasts, and Cancer: The Afterlife of an Idea (1924-2008)

Moss, R. W. — Tue, 30 Dec 2008 03:59:31 PST

In the early 20th century, advocacy of the enzyme therapy of cancer was primarily the work of one man, John Beard, DSc (1858-1924). He and his collaborators made a determined effort to establish this mode of therapy, especially in the years 1905 to 1911. Despite a brief flowering of international interest, Beard's efforts came to naught. During the 20th century, there was a succession of American researchers who continued to investigate this topic. This included Marshall William McDuffie, MD (1882-1945), Frank LeForest Morse, MD (1876-1953), Franklin Lloyd Shively, MD (1887-1971), and William Donald Kelley (1926-2005). In central Europe, India, and other parts of the globe, the use of pancreatic enzymes as an adjuvant treatment for cancer has become a fairly routine practice, at least among those doctors who utilize complementary and alternative medicine (CAM). It is also a well-established method for reducing inflammation and mitigating the adverse effects of cytotoxic treatment.

Of Germ Cells, Trophoblasts, and Cancer Stem Cells

Burleigh, A. R. — Tue, 30 Dec 2008 03:59:31 PST

The trophoblastic theory of cancer, proposed in the early 1900s by Dr John Beard, may not initially seem relevant to current cancer models and treatments. However, the underpinnings of this theory are remarkably similar to those of the cancer stem cell (CSC) theory. Beard noticed that a significant fraction of germ cells never reach their final destination as they migrate during embryonic development from the hindgut to the germinal ridge. In certain situations, upon aberrant stimulation, these vagrant germ cells are able to generate tumors. Simplistically, the CSC theory surmises that a small population of tumorigenic cells exists, which initiate and maintain tumors, and these cells have a likely origin in normal stem cells. Both these theories are based on the potential of a single primitive cell to form a tumor. This has a major implication for cancer therapy, in that only a small percentage of cells need to be targeted to ablate a tumor.

Differential Effects of Serine Proteases on the Migration of Normal and Tumor Cells: Implications for Tumor Microenvironment

Elzer, K. L., Heitzman, D. A., Chernin, M. I., Novak, J. F. — Tue, 30 Dec 2008 03:59:31 PST

The supporting role of proteases in tumor progression and invasion is well known; however, the use of proteases as therapeutic agents has also been demonstrated. In this article, the authors report on the differential effects of exogenous serine proteases on the motility of tumor and normal cells. The treatment of normal and tumor cells with a single dose of pancreatic serine proteases, trypsin (TR) and chymotrypsin (CH), leads to a concentration-dependent response by cells, first accelerating and then slowing mobility. Tumor cells are 10 to 20 times more sensitive to exogenous TR/CH, suggesting that a single dose of proteases may cause discordant movements of normal and tumor cells within the tumor environment. The inhibitory effects of TR on cell motility are contradicted by thrombin (TH), particularly in the regulation of normal cells' migration. The purpose of this investigation was to ascertain the role of protease-activated receptors (PARs) in terms of normal and tumor cell motility. Duplicate treatments with proteases resulted in diminished mobility of both normal and tumor cells. Repeated application of TR and TH in 1-hour treatment intervals initially desensitizes cell surface PARs. However, cell surface PARs reappear regardless of subsequent protease treatments in both normal and tumor cells. The resensitization process is retarded in tumor cells when compared with normal cells. This is evidenced by lower expression of PARs as well as by their relocalization at the tumor cell surfaces. Under these conditions, normal cells remain responsive to exogenous proteases in terms of cell motility. Exogenous proteases do not modulate motility of repeatedly stimulated tumor cells, and consequently, the migration of tumor cells appears disconnected from the PAR signaling pathways. The use of activating peptides in lieu of the cognate proteases for a given PAR system indicated that proteases may act through additional targets not regulated by PAR signaling. We hypothesize that the divergent migration patterns of normal and tumor cells due to exposure to proteases is in part mediated by PARs. Thus, treatment with exogenous proteases may cause rearrangement of the tumor and stromal cells within the tumor microenvironment. Such topographical effects may lead to the inhibition of tumor progression and metastasis development.

Exogenous Proteases Confer a Significant Chemopreventive Effect in Experimental Tumor Models

Wald, M. — Tue, 30 Dec 2008 03:59:31 PST

In this monograph, the chemopreventive effects of enterally administered proteases (trypsin, chymotrypsin, and papain) have been documented in a series of animal experimental tumor models. The experimental evidence demonstrates a significant inhibition of growth of both the primary tumor and the metastatic disseminations. Survival in animals treated with proteases is significantly longer than in untreated animals. The results confirm the fundamental correlation between early initiation of therapy and consequent growth of the tumorous disease. Comparable results have been shown in solid tumors in animal models (melanoma and Lewis lung carcinoma) and in human tumors (pancreatic and breast cancers). In this article, details of the known mechanisms of systemic actions of enterally administered proteases are documented and their relationship with cancerogenesis is discussed.

Proteolytic Enzyme Therapy in Evidence-Based Complementary Oncology: Fact or Fiction?

Beuth, J. — Tue, 30 Dec 2008 03:59:31 PST

Systemic enzyme therapy was recently subjected to experimental investigations and to rigorous clinical studies in cancer patients. The designs of the relevant clinical cohort studies followed the guidelines of Good Epidemiological Practice and represent level IIB in evidence-based medicine (EBM). Scientifically sound experimental in vitro and in vivo investigations are far advanced and document promising immunological, anti-inflammatory, anti-infectious, and antitumor/antimetastatic activities of proteolytic enzyme mixtures (containing trypsin, chymotrypsin, and papain) or bromelain. EBM level II clinical studies, which are accepted by the European Union to show safety and efficacy of medical treatments, were performed to evaluate the benefit of complementary systemic enzyme therapy in cancer patients suffering from breast and colorectal cancers and plasmacytoma. These studies demonstrated that systemic enzyme therapy significantly decreased tumor-induced and therapy-induced side effects and complaints such as nausea, gastrointestinal complaints, fatigue, weight loss, and restlessness and obviously stabilized the quality of life. For plasmacytoma patients, complementary systemic enzyme therapy was shown to increase the response rates, the duration of remissions, and the overall survival times. These promising data resulted in an "orphan drug status" designation for a systemic enzyme product, which should motivate further studies on this complementary treatment.

An Annotated Bibliography of Works by John Beard

Moss, R. W. — Tue, 30 Dec 2008 03:59:31 PST

This article provides a bibliography of the scientific publications of John Beard, DSc (1858-1924). Beard was an English embryologist and cancer researcher of the late 19th and early 20th century, who devised the trophoblastic theory of cancer, a forerunner of today's theory of cancer stem cells. Beard was the author of more than 100 scientific articles and monographs, as well as the book The Enzyme Treatment of Cancer (1911). This is the first bibliography ever compiled of his scientific publications.