Integrative Cancer Therapies recent issues

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

Block, K. I. — 2008-12-30

Introduction to the John Beard Special Issue

Moss, R. W. — 2008-12-30

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

Moss, R. W. — 2008-12-30

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. — 2008-12-30

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

Moss, R. W. — 2008-12-30

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. — 2008-12-30

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. — 2008-12-30

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. — 2008-12-30

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. — 2008-12-30

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. — 2008-12-30

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.

Feel Better. Live Better. Get Better

Block, K. I. — 2008-09-23

Disclosure to Physicians of CAM Use by Breast Cancer Patients: Findings From the Women's Healthy Eating and Living Study

2008-09-23

Background. Physician awareness of their patients' use of complementary and alternative medicine (CAM) is crucial, particularly in the setting of a potentially life-threatening disease such as cancer. The potential for harmful treatment interactions may be greatest when a patient sees a CAM practitioner—perceived as a physician-like authority figure—but does not disclose this to their physician. Therefore, this study investigated the extent of nondisclosure in a large cohort of cancer patients. Methods. CAM use in participants of the UCSD Women's Healthy Eating and Living (WHEL) Study, a multicenter study of the effect of diet and lifestyle on disease-free and overall survival in women aged 18-70 years who had completed treatment for invasive breast cancer between 1995 and 2000, is investigated. Data regarding CAM use and disclosure were collected via a telephone-administered questionnaire in 2003-2004. This questionnaire asked about different CAM modalities, including those requiring a "skilled CAM practitioner" (acupuncturist, chiropractor, homeopath, or naturopath) for administration. Demographic data were obtained at the WHEL baseline clinic interview. Modality-specific disclosure rates were determined and a comparison of demographic variables of disclosers versus nondisclosers was conducted using ² tests for categorical variables, and t tests for continuous variables. Results. Of 3088 total WHEL participants, 2527 completed the CAM questionnaire. Of these, 2017 reported using some form of CAM. Of these, 300 received treatment from an acupuncturist, chiropractor, homeopath, or naturopath and also provided information on whether or not they disclosed this care to their conventional physician. The highest disclosure rate was for naturopathy (85%), followed by homeopathy (74%), acupuncture (71%), and chiropractic (47%). Among demographic characteristics, only education (P = .047) and study site (P = .039) were associated with disclosure. College graduates and postgraduates, in particular, were more likely to disclose CAM use to their physicians than those with lesser education. Conclusion. Overall, moderately high rates of physician disclosure of CAM use for all modalities except chiropractic were observed. Education and study site associations suggest that disclosure may be greater when CAM use is more prevalent and possibly more socially accepted. These findings underscore the importance of open, destigmatized patient—physician communication regarding CAM use.

Biological Mediators of Effect of Diet and Stress Reduction on Prostate Cancer

Saxe, G. A., Major, J. M., Westerberg, L., Khandrika, S., Downs, T. M. — 2008-09-23

Background. A 6-month pilot intervention trial was conducted to determine whether adoption of a plant-based diet, reinforced by stress reduction, could reduce the rate of prostate-specific antigen (PSA) increase, a marker of disease progression, in asymptomatic, hormonally untreated patients experiencing consistently increasing PSA levels after surgery or radiation. Methods. A pre—post design was used to examine (1) the effect of intervention on potential mediators of disease progression, including body composition and weight-related biomarkers (sex steroid hormones and cytokines), and (2) whether changes in these variables were associated with change in rate of PSA increase. The baseline rate of PSA increase (from the time of posttreatment recurrence to the start of intervention) was ascertained from medical records. Body composition and biomarkers were assessed at baseline (prior to intervention), during the intervention (3 months), and at the end of the intervention (6 months). Changes in body composition and biomarkers were determined and compared with rates of PSA increase over the corresponding time intervals. Results. There was a significant reduction in waist-to-hip ratio (P = .03) and increase in circulating sex hormone binding globulin (P = .04). The rate of PSA increase decreased from the preintervention period (PSA slope = 0.059) to the period from 0 to 3 months (PSA slope = 0.002, P < .01) and increased slightly, although not significantly, from 0 to 3 months to the period from 3 to 6 months (0.029, P = .43). Conclusions. Adoption of a plant-based diet and stress reduction may reduce central adiposity and improve the hormonal milieu in patients with recurrent PC. Changes in the rate of increase in PSA were in the same direction as changes in waist-to-hip ratio and opposite those of sex hormone binding globulin, raising the possibility that the effect of the intervention may have been mediated, in part, by these variables.

Role of Religiosity and Spirituality in Complementary and Alternative Medicine Use Among Cancer Survivors in California

2008-09-23

Objectives. Cancer survivors often turn to religion, spirituality, and complementary and alternative medicine (CAM) because they perceive these areas as being more holistic and patient-centered than conventional medicine. Because increased religiosity and spirituality have been found to be associated with higher CAM use in the general population, it was hypothesized that these factors would be important predictors of CAM use in cancer survivors. Design and Subjects. The study included a subsample of 1844 people with cancer or a history of cancer from the 2003 California Health Interview Survey of CAM, a cross-sectional survey of a population-based sample of adults in California. Prevalence and predictors of religious/spiritual forms of CAM (R/S CAM) and nonreligious/nonspiritual forms of CAM (non-R/S CAM) were compared. Multivariate logistic regression was used to identify the predictors of R/S CAM and non-R/S CAM. Results. Nearly two thirds of participants reported using at least 1 type of R/S CAM, and 85% reported ever using non-R/S CAM. The majority of cancer survivors reported that they were very/moderately religious or spiritual. Both religiosity and spirituality were strongly related to non-R/S CAM use, but in opposite directions. Very or moderately religious cancer survivors were less likely (odds ratio = 0.30; 95% confidence interval, 0.12-0.40) than nonreligious cancer survivors to use non-R/S CAM. In contrast, very or moderately spiritual cancer survivors were more likely (odds ratio = 2.42; 95% confidence interval, 1.16-6.02) than nonspiritual cancer survivors to use non-R/S CAM. Conclusions. The use of R/S CAM and non-R/S CAM is very high in cancer survivors. It may be helpful for clinicians to ascertain their patients' use of these types of CAM to integrate all forms of care used to managing their cancer.

Acute Exercise Protects Against Doxorubicin Cardiotoxicity

Wonders, K. Y., Hydock, D. S., Schneider, C. M., Hayward, R. — 2008-09-23

Numerous methods have been used to minimize the cardiotoxic effects of the chemotherapeutic agent doxorubicin (DOX), and most have had limited success. Chronic endurance exercise has been shown to protect against DOX cardiotoxicity, but little is known regarding the effects of acute exercise on DOX-induced cardiac dysfunction. Purpose. The purpose of this study was to determine the effects of a single bout of acute endurance exercise on the cardiac dysfunction associated with DOX treatment. Methods. Male Sprague-Dawley rats either performed an acute exercise bout on a motorized treadmill for 60 minutes at a maximal speed of 25 m/min with a 5% grade (EX) or remained sedentary (SED) 24 hours before receiving either a 15-mg/kg DOX bolus dose or saline (SAL). Cardiac function was then analyzed 5 days post injection using a Langendorff isolated perfused heart model. In addition, myocardial lipid peroxidation was analyzed as an indicator of oxidative stress. Results. Doxorubicin treatment alone (SED+DOX) promoted a significant decline in end-systolic pressure (—35%), left ventricular developed pressure (—59%), and the maximal rate of left ventricular pressure development (—43%) as well as a 45% increase in lipid peroxidation products when compared with SED+SAL (P < .05). Acute exercise 24 hours before DOX treatment, however, had a cardioprotective effect, as end-systolic pressure, left ventricular developed pressure, and the maximal rate of left ventricular pressure development were significantly higher in EX+DOX compared with SED+DOX (P < .05) and EX+DOX had similar levels of lipid peroxidation products as SED+SAL Conclusions. An acute exercise bout performed 24 hours before DOX treatment protected against cardiac dysfunction, and this exercise-induced cardioprotection may partly be explained by a reduction in the generation of reactive oxygen species.

Amelioration of Radiation-induced Hematological and Biochemical Alterations by Alstonia scholaris (a Medicinal Plant) Extract

Gupta, U., Jahan, S., Chaudhary, R., Pradeep Kumar Goyal, — 2008-09-23

The radioprotective efficacy of a hydro-alcoholic extracted material from the bark of Alstonia scholaris (ASE) was studied in mice against radiation-induced hematological and biochemical alterations. Swiss albino mice were administered ASE (100 mg/kg body weight/d for 5 consecutive day) orally prior to whole-body gamma irradiation (7.5 Gy). Radiation exposure resulted in a significant decline (P < .001) in erythrocytes and hemoglobin until the third day, following a gradual recovery (ie, day 7), but these values did not reach normal values during the remainder of the animals' life span. Hematocrit percentage declined significantly (P < .001) until day 15. In contrast, ASE-pretreated irradiated animals had significantly higher erythrocyte, hematocrit, and hemoglobin values than the irradiated controls. Furthermore, a significant elevation in lipid peroxidation level over normal was recorded in gamma-irradiated mice, whereas this increase was considerably lower in ASE-pretreated animals. Pretreatment with ASE caused a significant increase in glutathione levels in serum as well as in liver in comparison to irradiated animals. This study showed that ASE protects against radiation-induced hematological and biochemical alterations in Swiss albino mice.

Mistletoe in Conventional Oncological Practice: Exemplary Cases

Legnani, W. — 2008-09-23

Mistletoe therapy, a cancer treatment suggested by Rudolf Steiner in 1920, is a typical and specific anthroposophic therapy, but could become more important today in the field of mainstream medicine. This article analyzes some of the most typical effects of mistletoe therapy based on the experience of more than 100 cases. A few patients were chosen who appear exemplary of the opportunities offered by mistletoe therapy. Their clinical history demonstrates an improvement in clinical condition and performance status, better quality of life, improved psychological status, reduction of infective events, better tolerance of concomitant chemoradiotherapy, and even a direct reduction of tumor size. The conclusion is that the patients may be indicative for future prospective clinical studies designed to confirm a real efficacy of mistletoe in cancer therapy.

A Retrospective Evaluation of the Effects of Deuterium Depleted Water Consumption on 4 Patients with Brain Metastases from Lung Cancer

Krempels, K., Somlyai, I., Somlyai, G. — 2008-09-23

Hypotheses. Because of the number of sufferers and high mortality rate, the standard care and new therapeutic options in the treatment of brain metastasis from lung cancer are the subject of intense research. A new concept based on the different chemical and physical behavior of protium and deuterium affecting cell signaling and tumor growth has been introduced in the treatment of cancer patients. The aim of this study was to investigate the impact of deuterium depleted water (DDW) consumption in addition to conventional forms of therapy on the survival of lung cancer patients with brain metastasis. Study design. A series of 4 case histories was retrospectively evaluated. The patients were diagnosed with brain metastasis deriving from a primary lung tumor and started consuming DDW at the time of or after the diagnosis of the brain metastasis, which was inoperable or the surgical intervention did not result in complete regression. The primary objective was survival. Methods. The daily water intake of the patients was replaced with DDW, which complemented the conventional forms of treatment. Patients were consuming DDW for at least 3 months. The treatment was continued with DDW of 10 to 15 to 20 ppm lower deuterium (D) content every 1 to 2 months and thus a gradual decrease was maintained in the D-concentration in the patient's body. Results. DDW consumption integrated into conventional treatments resulted in a survival time of 26.6, 54.6, 21.9, and 33.4 months in the 4 patients, respectively. The brain metastasis of 2 patients showed complete response (CR), whereas partial response (PR) was detected in 1 patient, and the tumor growth was halted (no change or NC) in 1 case. The primary tumor of 2 patients indicated CR, and the lung tumor in 2 patients showed PR. Conclusions. DDW was administered as an oral anticancer agent in addition to conventional therapy, and noticeably prolonged the survival time of all 4 lung cancer patients with brain metastasis. We suggest that DDW treatment, when integrated into other forms of cancer treatment, might provide a new therapeutic option.

Review of the Best Case Series Methodology: Best Case Series Results of East-West Cancer Center

Hwa Seung Yoo, , Chong Kwan Cho, , Hong, M. S. — 2008-09-23

Purpose. To assess the efficacy of the best case series program methodology as a preliminary evaluation of complementary and alternative programs. Setting. East-West Cancer Center (EWCC) is a traditional oriental cancer center located in Daejeon, Korea. Cancer patients received Wheel balance therapy (WBT), which focuses on rediscovering homeostatic harmony with dietary therapy, metabolism-activating therapy, antiangiogenesis and immune system therapy, and controlled breathing and psychotherapy. Methods. Summaries of 6 cases in which patients showed longer survival without progression and were treated with WBT without conventional treatments were submitted for review to the National Cancer Institute (NCI) Office of Cancer Complementary and Alternative Medicine. Each case was then classified by the NCI review panel with pathologic confirmation of disease and radiologic confirmation of complete response or partial response not attributable to conventional treatments. Results. Two of 6 cases were classified as evaluable NCI best cases; the other 4 cases were classified as unevaluable. Except for a patient with squamous cell lung carcinoma, no patient showed further progression as of July 2007. Conclusion. The best case series program provides a preliminary evaluation of complementary and alternative medicine programs. But the method will only find treatments that have effects similar to those of conventional methods such as surgery, chemotherapy, and radiation therapy. Therefore, in future studies, BCSP reviewers should additionally consider assessing tumor dormancy and efficacy of combination therapies for Best Case qualification.

Therapeutic Actions of Melatonin in Cancer: Possible Mechanisms

Srinivasan, V., Spence, D W., Pandi-Perumal, S. R., Trakht, I., Cardinali, D. P. — 2008-09-23

Melatonin is a phylogenetically well-preserved molecule with diverse physiological functions. In addition to its well-known regulatory control of the sleep/wake cycle, as well as circadian rhythms generally, melatonin is involved in immunomodulation, hematopoiesis, and antioxidative processes. Recent human and animal studies have now shown that melatonin also has important oncostatic properties. Both at physiological and pharmacological doses melatonin exerts growth inhibitory effects on breast cancer cell lines. In hepatomas, through its activation of MT₁ and MT₂ receptors, melatonin inhibits linoleic acid uptake, thereby preventing the formation of the mitogenic metabolite 1,3-hydroxyoctadecadienoic acid. In animal model studies, melatonin has been shown to have preventative action against nitrosodiethylamine (NDEA)-induced liver cancer. Melatonin also inhibits the growth of prostate tumors via activation of MT₁ receptors thereby inducing translocation of the androgen receptor to the cytoplasm and inhibition of the effect of endogenous androgens. There is abundant evidence indicating that melatonin is involved in preventing tumor initiation, promotion, and progression. The anticarcinogenic effect of melatonin on neoplastic cells relies on its antioxidant, immunostimulating, and apoptotic properties. Melatonin's oncostatic actions include the direct augmentation of natural killer (NK) cell activity, which increases immunosurveillance, as well as the stimulation of cytokine production, for example, of interleukin (IL)-2, IL-6, IL-12, and interferon (IFN)-. In addition to its direct oncostatic action, melatonin protects hematopoietic precursors from the toxic effect of anticancer chemotherapeutic drugs. Melatonin secretion is impaired in patients suffering from breast cancer, endometrial cancer, or colorectal cancer. The increased incidence of breast cancer and colorectal cancer seen in nurses and other night shift workers suggests a possible link between diminished secretion of melatonin and increased exposure to light during nighttime. The physiological surge of melatonin at night is thus considered a "natural restraint" on tumor initiation, promotion, and progression.

Granulosa Cell Tumor of the Ovary: Tumor Review

2008-09-23

Granulosa cell tumors of the ovary are rare neoplasms that originate from sex-cord stromal cells. The long natural history of granulosa cell tumors and their tendency to recur years after the initial diagnosis are the most prominent of their characteristics. The secretion of estradiol is the reason for signs at presentation such as vaginal bleeding and precocious puberty. Abdominal pain and hemoperitoneum, which occasionally can occur, are attributable to tumor rupture. The most common finding in pelvic examination is a tumor mass, which is subsequently confirmed with imaging techniques. Surgery is the mainstay of initial management for histological diagnosis, appropriate staging, and debulking. A more conservative unilateral salpingo-oophorectomy is indicated in patients with stage I disease and patients of reproductive age. Total abdominal hysterectomy with bilateral salpingo-oophorectomy is the appropriate surgical treatment for postmenopausal women and those with more advanced disease. The stage of disease is the most important prognostic factor associated with the risk of relapse. There are no clear conclusions regarding the role of postoperative chemotherapy or radiotherapy in stage I disease and in those with completely resected tumor. The use of adjuvant chemotherapy or radiotherapy has sometimes been associated with prolonged disease-free survival and possibly overall survival. Chemotherapy is the treatment of choice for patients with advanced, recurrent, or metastatic disease, and BEP (bleomycin, etoposide, and cisplatin) is the preferred regimen. Although the overall rate of response to treatment is high, the impact of treatment on disease-free or overall survival is unknown. Prolonged surveillance is mandatory because tumors tend to recur years after the initial diagnosis.

An Antioxidant Turnabout

Block, K. I. — 2008-06-11

Facing the Challenges of Hematopoietic Stem Cell Transplantation With Mindfulness Meditation: A Pilot Study

2008-06-11

The hematopoietic stem cell transplant (HSCT) experience is emotionally and physically stressful for cancer patients who undergo this procedure. Mindfulness-based interventions have been studied in patients with various diagnoses, including cancer, although minimal work has applied this intervention to hospitalized patients. Use of mindfulness meditation has potential to provide HSCT patients with coping skills to deal with unpleasant symptoms and an uncertain future. This exploratory study examined feasibility, physiological arousal, and psychological and physical symptoms in HSCT patients participating in a mindfulness meditation intervention that begins before and continues throughout hospitalization and involves one-on-one guided sessions and daily practice using a 17-minute meditation CD. Of the 20 participants, 78.9% completed the intervention. Statistically significant decreases in heart and respiratory rates and improvements in symptoms immediately before and after each session were found. These findings demonstrate feasibility and preliminary support of a mindfulness meditation intervention with symptomatic, hospitalized cancer patients.

An International Pilot Study of Oncology Physicians' Opinions and Practices on Complementary and Alternative Medicine (CAM)

Lee, R. T., Hlubocky, F. J., Hu, J.-J., Stafford, R. S., Daugherty, C. K. — 2008-06-11

Background. In China and Taiwan, Complementary and Alternative Medicine (CAM) therapies such as traditional Chinese medicine have been an option to cancer patients for centuries, whereas in the United States, CAM has been growing in popularity only in the past few decades. Prior research has indicated that the prevalence of CAM use among cancer patients may exceed 80%. Because of a long cultural history of CAM, we hypothesized that oncologists in China and Taiwan (C/T) would communicate and combine CAM with conventional treatments more often than US oncologists. Methods. In 2004-2005, a convenience sample of oncologists from the United States, mainland China, and Taiwan were surveyed regarding their opinions and self-reported practice patterns regarding CAM. Results. A total 95 oncologists returned surveys, providing a 38% response rate. Four out of 5 respondents (78%) felt their medical training was inadequate to use CAM. However, 70% reported they would allow CAM use during active cancer treatment, even in the setting of curable disease. Responding C/T oncologists tended to ask patients more frequently (they ask > 25% of patients) about CAM use and recommended CAM more commonly (recommend to > 10%) to patients than surveyed US oncologists, 55% versus 37% (P = .09) and 81% versus 53% (P < .05). Respondents from the United States felt no more prepared for CAM use than C/T respondents, but 70% reported willingness to combine CAM with conventional treatments for curable disease as compared with only 48% (P < .05) of C/T oncologists. Conclusions. As expected, responding C/T oncologists communicate more often about CAM with patients by asking and recommending CAM. However, contrary to our original hypothesis, C/T oncologists reported a much lower rate of combining CAM with conventional treatment among curable patients than responding US oncologists. Further research is needed to explore, in depth, the reasons for differences in CAM practice patterns among oncologists.

Human Ovarian Carcinomas Detected by Specific Odor

Horvath, G., Jarverud, G. a. K., Jarverud, S., Horvath, I. — 2008-06-11

The high mortality rate associated with ovarian carcinoma is mainly owing to late diagnosis. It is thus essential to develop inexpensive and simple methods for early diagnosis. Papers on canine scent detection of malignancies such as melanoma and bladder, lung, and breast cancer have recently been published in peer-reviewed journals, indicating a new diagnostic tool for malignancies. However, in these studies the dogs may have responded to odors associated with cancer, such as inflammation or metabolic products, rather than specifically to cancer itself. Therefore, it is important to ascertain whether or not human cancers are characterized by specific odors. We hypothesized that if ovarian carcinoma emits a specific odor, dogs may be trained to detect it. Using our training method, we taught a dog to distinguish different histopathological types and grades of ovarian carcinomas, including borderline tumors, from healthy control samples. Double-blind tests showed 100% sensitivity and 97.5% specificity. Moreover, the odor of ovarian carcinomas seems to differ from those of other gynecological malignances such cervical, endometrial, and vulvar carcinomas. Our study strongly suggests that the most common ovarian carcinomas are characterized by a single specific odor.

Shedding Light on Vitamin D and Integrative Oncology

Cantor, I. — 2008-06-11

Studies show an important relationship between vitamin D and malignancies, both in prevention and treatment. The extraskeletal actions of vitamin D relevant to oncology include being proapoptotic, antimetastatic, antiangiogenic, antiinflammatory, prodifferentiating, and immunomodulating. Widespread and severe vitamin D deficiencies exist worldwide. Decreased sun exposure, caused by lifestyle changes, as well as fear of skin cancers, is the main cause of these deficiencies. Recommended daily oral intakes, as well as suggested blood levels, are below optimal levels suggested by studies. Improvement in vitamin D status, through lifestyle changes and supplementation, can be of profound benefit regarding the occurrence and mortality of malignancies.

Tumor Versus Tumor-Associated Macrophages: How Hot is the Link?

Guruvayoorappan, C. — 2008-06-11

One of the functions of macrophages is to provide a defense mechanism against tumor cells. In contrast, tumor-associated macrophages (TAMs), which represent the major inflammatory component of the stroma of many tumors, are associated with tumor progression and metastasis. TAMs, in contrast with normal macrophages, exhibit the M2 phenotype, and thereby exhibit pro-tumoral functions, including angiogenesis and matrix remodeling. This review will discuss the role of TAMs in tumor progression and provide an overview of their significant part in tumor metastasis and angiogenesis.

The Tumoricidal Effect of Sonodynamic Therapy (SDT) on S-180 Sarcoma in Mice

Xiaohuai Wang, , Lewis, T. J., Mitchell, D. — 2008-06-11

There are increasing data showing that sonodynamic therapy (SDT), which refers to a synergistic effect of drugs and ultrasound, is a promising new modality for cancer treatment. However, few clinical data on SDT have been published. One reason is the lack of suitable drugs for clinical SDT use. Recently a new sonosensitizing agent has been developed by SonneMed, LLC, referred to as SF1. In this study the effect of SDT with SF1 on S-180 sarcoma in mice was examined. The tumor bearing mice were allocated to the following groups: (1) sham-treatment (control, C); (2) ultrasound treatment (only ultrasound treatment, 1.2 mW/cm² , without SF1, U); (3) SF1 treatment (SF1 20 mg/kg intraperitoneal [ip] without ultrasound treatment, S); and (4) SF1 + ultrasound treatment (SU). Following treatment, tumor volume was monitored. Tumor growth inhibition was seen only in group SU, and with increasing ultrasound intensity, the inhibitory effect was enhanced. Tumor growth inhibition was also visible even when covered by a barrier of bone. Pathological slices showed coagulated necrosis or metamorphic tissue with inflammatory reaction in the tumor taken from 2 to 36 hours after SDT. These data revealed that SDT with SF1 did inhibit growth of mouse S-180 sarcoma and the inhibitory effect was sound intensity dependent. SDT also induced some inflammation while it destroyed the tumor, indicative of a "vaccine" effect. SF1 shows great promise for clinical use in the future.

Integrative Tumor Board: Pancreatic Cancer Case Presentation

Gyllenhaal, C. — 2008-06-11

Integrative Tumor Board: Pancreatic Cancer Naturopathic Medicine

Alschuler, L., Rubin, D. — 2008-06-11

Integrative Tumor Board: Pancreatic Cancer Physical Therapy

Kranz, S. — 2008-06-11

Integrative Tumor Board: Pancreatic Cancer Pastoral Counseling

Roddy, G. D. — 2008-06-11

Integrative Tumor Board: Pancreatic Cancer Integrative Physician's Perspective

Block, K. I. — 2008-06-11

Cancer's Impact on Social Roles

Block, K. I. — 2008-02-21

Using Mixed Methods for Evaluating an Integrative Approach to Cancer Care: A Case Study

Brazier, A., Cooke, K., Moravan, V. — 2008-02-21

Objective. To evaluate the impact of participating in an integrative cancer care program at the Centre for Integrated Healing in Vancouver, British Columbia, on patients' lifestyle, quality of life, and overall well-being. Study Design. A mixed-methods case study with a pre- and posttest design. No control group was utilized. Methods. All new patients starting at the Centre for Integrated Healing between May and September of 2004 were invited to join the study. Forty-six of 77 new patients agreed to participate. Quantitative data measuring quality of life, social support, anxiety and depression, locus of control, and hope were assessed at baseline (pre-program start) and at 6 weeks and 5 months from the start of the program. Qualitative data in the form of focus groups and interviews were collected midway through the follow-up period to further explore program impacts. Results. No statistically significant improvements or declines were noted on the quantitative measures between baseline and the 5-month follow-up point. The qualitative findings revealed a theme of patients' active engagement in their cancer care involving empowered decision making and creating personal change. Facilitators of active patient engagement in their own care from the integrative program included healing partnerships with practitioners, information and resources, managing the integration of complementary and conventional therapies, emotional support, and a sense of hope. Discussion. This case study was a first attempt at documenting the impact of an integrative cancer care program at the Centre for Integrated Healing. Study limitations included a small sample size, which limited power to detect quantitative changes on the questionnaires and a lack of a control group. Qualitative findings indicated that patients found value in the "person-oriented" holistic approach to care, which encouraged patients to take an active role in decision making and self-care. The use of a mixed-methods research design proved to be an effective approach to not only evaluating outcomes but also examining process issues of the experience. Additional research is greatly needed to better understand potential impacts of integrative approaches to cancer care.

The Effect of a Complex Healing Treatment on 2-Year Survival Rate of Patients With Malignant Tumors

He Xiaomei, , Fan Jingchuan, — 2008-02-21

Purpose. The purpose of this study is to discuss the effect of an intervention measure combining oncology, psychology, and sociomedicine on survival and quality of life in cancer patients. Methods. 639 cases of malignant tumor were divided into intervention and control groups. Follow-up was completed on 254 cases in the intervention group (93.38%) and 330 cases in the control group (89.91%). The intervention consisted of systematic mass anticancer education and rehabilitation activities guided by specialists over the period of 2 years, while the control group was in a state of self-rehabilitation. Differences between groups in survival status and survival rate for different disease stages were reviewed after 2 years. Survival status was evaluated by the Cox proportional hazards model. Results. Statistical analysis of survival was controlled for sociological variables such as marriage and age. The 2-year survival in stage 2 patients was 94.84% (108/114) in the intervention group and 80.67% (121/150) in the control group. There was a striking and significant (P < .01) difference in 2-year survival rates. Further analysis disclosed that 2-year survival rate for early- and medium-stage patients was 88.03% (163/177) in the intervention group and 82.8% (184/222) in the control group. Conclusion . An intervention including oncology, psychology, and sociomedicine improved 2-year survival rate in early and middle stages of malignant tumor.

Clinical Encounter Experiences of Patients With Nasopharyngeal Carcinoma

Lee, E. W. C., Twinn, S., Moore, A. P., Jones, M. P., Leung, S.F. — 2008-02-21

Nasopharyngeal carcinoma (NPC) is a commonly occurring cancer among Hong Kong Chinese, especially in the relatively young population group. Since the disease carries a favorable prognosis, sequelae following treatment have become an important concern for patients suffering from NPC, particularly because of the strong interplay of psychological, social, and biological issues during their rehabilitation. In this qualitative study, in-depth, semistructured audiotaped interviews were undertaken with 32 patients receiving rehabilitation at the physiotherapy department of a regional teaching hospital in Hong Kong. The objective of the study was to examine the rehabilitation experiences of NPC survivors to identify factors that contributed to a satisfying clinical encounter experience. During the study, data collection and analysis using a grounded theory approach were concurrently conducted. The 3 main themes that shaped the rehabilitation experiences of NPC survivors were the patient-clinician relationship, participation in therapeutic alliance, and quality rehabilitation service provision. These, together with the identified needs of the participants, contributed to the participants' perceived health-related quality of life. A constructive clinical experience was perceived when their needs were met. The findings highlight the importance of patient-centeredness in the treatment delivery and a multifaceted role of clinicians in meeting the needs of this group of cancer survivors.

Significance of Alterations in Plasma Lipid Profile Levels in Breast Cancer

2008-02-21

Hypotheses. The relationship between lipids and breast cancer is obscure. Until now, conflicting results have been reported on the association between lipids and risk of breast cancer in women. Therefore, the major aim of this study is to examine the role of alterations in lipid profile in breast cancer. Study Design. Plasma lipids (ie, total cholesterol [TC], high-density lipoprotein [HDL], low-density lipoprotein [LDL], very-low-density lipoprotein [VLDL], and triglycerides [TG]) were analyzed from 70 controls, 30 patients with benign breast disease (BBD), 125 untreated breast cancer patients, and 93 posttreatment follow-up samples. Methods. Samples were analyzed using highly sensitive and specific spectrophotometric methods. Results. Plasma TC, LDL, VLDL, and TG were significantly lower (p = .042, p = .003, p = .024, p = .014, respectively) in patients with BBD compared with controls. Plasma TC and HDL were significantly lower (p = .026, p = .0001, respectively), and VLDL and TG were significantly higher (p = .009, p = .05) in breast cancer patients as compared with controls. Plasma VLDL and TG were significantly higher in breast cancer patients as compared with patients with BBD. The receiver-operating characteristic curve showed that plasma TC, LDL, VLDL, and TG levels could significantly discriminate (p = .001, p = .005, p = .005, p = .005, respectively) between controls and patients with BBD. Plasma levels of TC, HDL, VLDL, and TG could significantly distinguish (p = .01, p = .002, p = .001, p = .002, respectively) between controls and breast cancer patients. Plasma levels of VLDL and TG could significantly discriminate (p = .000, p = .000, respectively) between patients with BBD and breast cancer patients. Odds ratio analysis revealed that higher levels of TC and HDL were significantly associated with a reduction in breast cancer risk (p = .01 and p = .0001, respectively), whereas higher levels of VLDL and TG were significantly associated with increased breast cancer risk (p = .001 and p = .002, respectively). Plasma VLDL and TG levels were significantly lower in complete responders as compared with pretreatment levels (p = .000, p = .000, respectively), and plasma TC and LDL levels were significantly lower in nonresponders as compared with pretreatment levels (p = .015, p = .009, respectively). Conclusion. The alterations in lipid profile levels showed a significant correlation with breast cancer risk, disease status, and treatment outcome.

Biophytum sensitivum (L.) DC Inhibits Tumor Cell Invasion and Metastasis Through a Mechanism Involving Regulation of MMPs, Prolyl Hydroxylase, Lysyl Oxidase, nm23, ERK-1, ERK-2, STAT-1, and Proinflammatory Cytokine Gene Expression in Metastatic Lung Tissue

Guruvayoorappan, C., Kuttan, G. — 2008-02-21

Biophytum sensitivum is a traditional oriental herbal medicine that is known for its immunostimulatory and antitumor effects. Tumor metastasis is the most important cause of cancer death. Although B sensitivum was shown to inhibit metastasis, the mechanism underlying this action is not well understood. In the present report, the authors had studied the effect of B sensitivum on the invasion and motility of B16F-10 melanoma cells and investigate the regulatory effect on the expression of matrix metalloproteases (MMPs), prolyl hydoxylase, lysyl oxidase, nm23, extracellular signal-regulated kinase (ERK)—1, ERK-2, signal transducer and activator of transcription (STAT)—1, and proinflammatory cytokines in metastatic tumor-bearing lungs. B sensitivum inhibited the invasion and motility of B16F-10 cells in a dose-dependent manner. B sensitivum inhibited the expression of MMP-2 and MMP-9, whereas it activated STAT-1 expression in metastatic tumor-bearing lungs. Similarly, inhibition of prolyl hydroxylase, lysyl oxidase, ERK-1, ERK-2, and vascular endothelial growth factor (VEGF) expression but activation of nm23 by B sensitivum was observed in metastatic tumor-bearing lungs. B sensitivum treatment also downregulated the expression of tumor necrosis factor—, interleukin (IL)—1β, IL-6, and granulocyte monocyte—colony stimulating factor in metastatic tumor-bearing lungs. In B16F-10 cells, B sensitivum also inhibited the production of proinflammatory cytokines. Overall, the results indicate that B sensitivum exhibits antimetastatic effects through the inhibition of invasion and motility. The results also suggest that MMPs, prolyl hydroxylase, lysyl oxidase, nm23, ERKs, VEGF, STAT, and proinflammatory cytokines are critical regulators of the B sensitivum—mediated antimetastatic effect.

Arterial Chemotherapy and Conformal Radiation Abolish Malignant Biliary Obstruction

Guan, Y.-S., Qing He, , Ping Li, , Fu, Y.-C., Zhao, S.-W. — 2008-02-21

Malignant biliary obstruction has been a challenge to clinical practitioners, especially when it is serious and complete. Chemotherapy or radiation alone is often unsuccessful. In this study, the authors report a 59-year-old patient with complete common bile duct obstruction caused by cholangiocarcinoma who was treated with arterial chemotherapy followed by 3-dimensional conformal radiation, which resulted in a good clinical outcome.