Integrative Cancer Therapies

The 11th International Conference of the Society for Integrative Oncology (SIO) brought together more than 300 clinicians, researchers, patients, and advocates to hear and interact with world-leading experts about the latest research in the areas of nutrition, exercise, acupuncture, health services research, meditation, and other integrative disciplines. The conference theme, "Personalized Integrative Oncology: Targeted Approaches for Optimal Outcomes," highlighted innovations in personalized medicine and ways this growing field will advance the evolution of individualized integrative cancer care to the next level. This year's conference also featured a clinical track focusing on clinical information for the practicing health care professional. The conference's rigorous schedule included 3 keynotes, 4 plenary sessions, 2 interdisciplinary tumor boards, 5 workshops, 45 concurrent oral sessions, and 106 posters. In addition to the conference theme, keynote and plenary sessions presented topics on stress and cancer, the importance of sleep for cancer patients, epigenetic mechanisms of lifestyle and natural products, recently published Journal of the National Cancer Institute monograph on integrative oncology, SIO's clinical practice guidelines for breast cancer survivors, and a joint session of the American Academy of Hospice and Palliative Medicine and SIO about supportive care and symptom management. This highly successful conference helped further the mission of the SIO to advance evidence-based, comprehensive, integrative health care to improve the lives of people affected by cancer. © The Author(s) 2014.

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. 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. 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. 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.

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.

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.

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.

The ancient system of Kundalini Yoga (KY) includes a vast array of meditation techniques. Some were discovered to be specific for treating psychiatric disorders and others are supposedly beneficial for treating cancers. To date, 2 clinical trials have been conducted for treating obsessive-compulsive disorder (OCD). The first was an open uncontrolled trial and the second a single-blinded randomized controlled trial (RCT) comparing a KY protocol against the Relaxation Response and Mindfulness Meditation (RRMM) techniques combined. Both trials showed efficacy on all psychological scales using the KY protocol; however, the RCT showed no efficacy on any scale with the RRMM control group. The KY protocol employed an OCD-specific meditation technique combined with other techniques that are individually specific for anxiety, low energy, fear, anger, meeting mental challenges, and turning negative thoughts into positive thoughts. In addition to OCD symptoms, other symptoms, including anxiety and depression, were also significantly reduced. Elements of the KY protocol other than the OCD-specific technique also may have applications for psycho-oncology patients and are described here. Two depression-specific KY techniques are described that also help combat mental fatigue and low energy. A 7-part protocol is described that would be used in KY practice to affect the full spectrum of emotions and distress that complicate a cancer diagnosis. In addition, there are KY techniques that practitioners have used in treating cancer. These techniques have not yet been subjected to formal clinical trials but are described here as potential adjunctive therapies. A case history demonstrating rapid onset of acute relief of intense fear in a terminal breast cancer patient using a KY technique specific for fear is presented. A second case history is reported for a surviving male diagnosed in 1988 with terminal prostate cancer who has used KY therapy long term as part of a self-directed integrative care approach.

Hyperglycemia is commonly manifested in cancer patients. Although high intakes of sugar and refined carbohydrates and elevated blood glucose are strongly associated with the risk of cancer, much less is known about their effects on survival after cancer diagnosis. There is evidence that high carbohydrate intake is associated with poorer survival after diagnosis for early breast cancer. We measured glycated hemoglobin in a group of cancer patients (some with active disease and some in remission) and found a statistically significant lower average blood glucose in those in remission. Glycated hemoglobin provides an indication of average blood glucose over 2 to 3 months. The authors discuss lifestyle changes including diet and physical activity that can reduce average blood glucose. Ascorbic acid (AA) supplementation as an adjunct to cancer therapy is also considered. Furthermore, they present a biologically plausible explanation for how hyperglycemia can impair the actions of AA and damage immune effectiveness and hinder cancer survival. One mechanism is likely a reduction in intracellular AA; high intracellular levels of AA are necessary for optimal activity of the hexose monophosphate shunt. This metabolic pathway is important for maintaining proper cellular antioxidant status in immune cells including lymphocytes involved in cell-mediated immunity.

In 1993, a 54-year-old woman was diagnosed with early-stage breast adenocarcinoma and treated with doxorubicin and cyclophosphamide followed by tamoxifen. Nine years later, the patient presented for integrative treatment, with liver metastases. Carcinoembryonic antigen was significantly elevated. The patient was started on a heavily fractionated, multiple-agent chemotherapy regimen; however, she underwent significant adverse effects and the treatment was suspended. She then started on intravenous nutrition along with specific nutritional supplements. Two months later, a similar chemotherapeutic regimen was started in association with her existing nutritional protocol. One month later, the carcinoembryonic antigen began to rise, and a positron emission tomography scan was ordered that revealed the persistence of multiple and extensive liver metastases as well as possible skeletal metastases. The patient was started on an oral bisphosphonate and referred to interventional radiology for consultation on radioembolization with yttrium-90. After being accepted for treatment, the patient under-went a right hepatic lobe angiogram and radioembolization. Within 2 weeks, she realized significant improvements in her clinical and laboratory status; chemotherapy was discontinued. She later underwent radioembolization to her left lobe. Thirteen months after the yttrium-90 treatment, the patient remains on an integrative program with radiographically and clinically stable disease.

Vitexina, a product containing the flavonoid vitexin as the main component, is derived from a plant, Vigna radiata (L.), that has been traditionally used in Vietnam for detoxification. This remedy is also used to treat the symptoms of conditions classified as "hot" in traditional medicine. The present study is a randomized, placebo-controlled comparative clinical trial for investigating the radioprotective effects of Vitexina for breast cancer patients undergoing radiotherapy with cobalt-60. No relevant weight loss, (even weight gain), occurred in 70% of patients in the Vitexina group, whereas 73% of the placebo group lost 1 to 2 kg of weight after 6 weeks of radiation therapy. The administration of Vitexina produced a significantly protective effect in peripheral blood cells in amount and in lymphocyte blast-transformation function. Condition of hot was observed in almost all cancer patients in this study by tongue examination. Hot condition did not change in the Vitexina group, but the incidence of hot and extreme hot cases were significantly increased in the placebo group after 6 weeks of radiation therapy. The results suggest that application of medicinal plants of the "clearing heat and detoxification" classification as an adjuvant would be a potential solution in integrative cancer therapy.

Purpose: The study was designed to screen Sphaeranthus indicus, Ganoderma lucidum, and Urtica dioica for their anticancer activity against human cancer cell lines. Phytochemical screening of active extracts was also planned. Methods: Petroleum ether, ethanolic, and aqueous extracts of S indicus Linn, G lucidum P Karst, and U dioica Linn were subjected to cytotoxicity studies using 7 different cancer cell lines. Potent cytotoxicity was noted in petroleum ether extract of S indicus (SIP), which inhibited proliferation of various cancer cell lines. Growth inhibition was determined by sulforhodamine B assay. Two biochemical markers, namely β-sitosterol and 7-hydroxyfrullanolide were isolated and characterized using high-performance thin layer chromatography, melting point, Fourier transform infrared spectroscopy, nuclear magnetic resonance spectroscopy, and mass analysis. Cytotoxicity of isolated β-sitosterol and 7-hydroxyfrullanolide were also determined. The IC(50) of SIP was calculated in the HL-60 cells and was found to be 53 µg/mL. Furthermore, SIP induced apoptosis in human leukemia HL-60 cells as measured by several biological end points. Cell cycle analysis and change in mitochondrial membrane potential was quantified by flow cytometry. Subsequently, using annexin V/PI assay, proportion of cells actively undergoing apoptosis was determined. Changes in DNA were observed by DNA ladder assay. Results: SIP induced apoptotic bodies formation, induced DNA laddering, enhanced annexin-V-FITC binding of the cells, increased sub-G(0) DNA fraction, and induced loss of mitochondrial membrane potential (ΔΨm) in HL-60 cells. SIP also elevated the caspase 3 and caspase 9 levels in the HL-60 cells, which clearly indicates the involvement of the intrinsic proteins in inducing apoptosis. Discussion: All the above parameters revealed that SIP induced apoptosis through the mitochondrial-dependent pathway in HL-60 cells. The criterion for anticancer activity in cytotoxicity assay was ≥70% growth inhibition at 100 µg/mL against at least 4 cell lines. As G lucidum and U dioica did not exhibit appreciable inhibitory activity against human cancer cell lines (less than 50%), they were not included in the study thereafter. The results established that SIP has apoptosis-inducing effect against HL-60 cells in vitro and is a promising candidate for further anticancer study. β-Sitosterol and 7-hydroxyfrullanolide can be considered to be potent anticancer compounds isolated from SIP on the basis of present studies.

The present investigation was undertaken to explore the antitumor-promoting activity of Aloe vera on 2-stage skin carcinogenesis, induced by a single topical application of 7,12-dimethylbenz(a)anthracene and promoted by treatment of croton oil for 16 weeks in Swiss albino mice. Oral administration of aloe leaf extract at a dose of 1000 mg/kg body weight/d and aloe gel treatment at a dose of 1 mL/9 cm(2)/mice/d was found to be effective in decreasing the number and size of the papillomas. A significant reduction in tumor incidence (40.00+/-5.10, 30.00+/-3.25, and 40.00+/-4.12 for aloe gel, aloe gel and aloe leaf extract combined, and aloe leaf extract alone, respectively) was observed in animals in the aloe extract- and aloe gel-treated groups compared with 100% tumor incidence in the control group. The cumulative number of papillomas during an observation period of 16 weeks was significantly reduced in the aloe-treated groups (8.0+/-0.34, 6.00+/-1.10, and 9.00+/-1.41 for aloe gel, aloe gel and leaf extract, and aloe leaf extract, respectively) compared with a 36+/-0.98 cumulative number of papillomas in the control group. The average latent period was significantly increased from 4.9+/-0.10 weeks in the control group to 6.37+/-0.12, 6.8+/-0.25, and 6.2+/-0.21 weeks in the aloe-treated groups, respectively. The tumor burden and tumor yield were significantly decreased (2.0+/-0.25, 2.00+/-0.30, and 2.25+/-0.2 and 0.8+/-0.25, 0.6+/-0.32, and 0.9+/-0.28, respectively) as compared with the 7,12-dimethylbenz(a)anthracene-treated control group (3.6+/-0.10 and 3.6+/-0.19). Furthermore, treatment with aloe gel and/or extract by topical and/or oral administration resulted in a significant increase in the reduced glutathione (P< .05), DNA (P< .001), catalase (P< .05), and protein (P< .001) in the skin of mice. Conversely, lipid peroxidation levels were significantly decreased (P< .001) in the skin of mice.

This study was designed to investigate the anticancer activity of extracts of the phytomedicine DAS-77. The sulforhodamine B (SRB) in vitro cytotoxicity assay, Sarcoma-180 (S-180) ascites and solid tumor, and L1210 lymphoid leukemia in vivo models were employed. DAS-A001 (ethanol extract, IC50 12 and 13 µg/mL with HCT-116 and PC3, respectively); DAS-A002 (hydroethanol extract, IC50 <5 and 13 µg/mL with HCT-116 and PC3, respectively); DAS-A003 (aqueous extract, IC50 <5 µg/mL with THP-1); and DAS-A004 (dichloromethane:methanol extract; IC50 <5 and 17 µg/mL with HCT-116 and PC3, respectively) demonstrated significant activity in vitro. DAS-A002 and DAS-A003 (80-120 mg/kg) elicited significant (P < .05-.001) dose-dependent inhibition of tumor growth in the S-180 ascites model. Peak effects were produced at the highest dose of 120 mg/kg with inhibition values of 87.50% and 89.23% for DAS-A002 and DAS-A003, respectively, compared with a value of 97.27% for 5-FU (20 mg/kg). As regards the S-180 solid tumor model, inhibition of tumor growth was found to be 52.56% and 37.95%, respectively, for DAS-A002 and DAS-A003. The effect of DAS-A002 was comparable and not significantly different (P > .05) from that of 5-FU (20 mg/kg; 50.18% inhibition). DAS-A003 but not DAS-A002 showed significant activity in the leukemia model with 177.78% increase in mean survival time relative to 211.11% for 5-FU. Findings in this study suggest that the hydroethanol and aqueous extracts of DAS-77 possess significant anticancer activity.

The objective of this study was to investigate the reversal effect of Chinese herbs of Shenghe Powder on the multidrug resistance of the human SGC-7901 gastric carcinoma cell line and vincristine-resistant cell line (SGC-7901/vincristine) and the possible mechanism. SGC-7901 and SGC-7901/ vincristine were cultured in liquid medium RMPI 1640, with the addition of vincristine to the vincristine-resistant line. The reversal effect of Shenghe Powder (using verapamil as control) on the multidrug resistance of SGC-7901/vincristine cells was observed using the 3-4,5-dimethylthiazol-2yl) -2,5-diphenylterazolium bromide method. The expression rate of P-glycoprotein (P-gp), lymphoma/leukemia-2 (Bcl-2), and apoptosis ratio of SGC-7901 and SGC-7901/vincristine with added Shenghe Powder, verapamil, or verapamil plus Shenghe Powder was observed by flow cytometry. Shenghe Powder and verapamil decreased the multidrug resistance of SGC-7901/vincristine. The effect of Shenghe Powder (10 mg/L) was significantly higher than verapamil (P< .05). The intracellular concentration of vincristine was increased by Shenghe Powder and verapamil. The vincristine concentration of SGC-7901/vincristine treated with Shenghe Powder was significantly higher (P< .05). Shenghe Powder reduced the expression level of P-gp and Bcl-2 in SGC-7901/ vincristine and increased the apoptotic percentage of tumor cells; Shenghe Powder had the more significant effect on apoptosis (P< .05). In conclusion, Shenghe Powder increases the intracellular concentration of vincristine, consistent with the down-regulation of the expression of P-gp and Bcl-2. The reversal effect of Shenghe Powder was stronger than that of verapamil.

Primitive neuroectodermal tumors (PNETs) are usually successfully treated with craniospinal radiation and chemotherapy; however, difficulties with standard treatment can be encountered in very young children, in adult patients at high risk of complication from standard treatment, and in patients with recurrent tumors. Thirteen children, either with recurrent disease or high risk, were treated in phase II studies with antineoplastons (ANP). The median age of patients was 5 years, 7 months (range, 1-11). Medulloblastoma was diagnosed in 8 patients, pineoblastoma in 3 patients, and other PNET in 2 patients. Previous treatments included surgery in 12 patients (1 had biopsy only, suboccipital craniotomy), chemotherapy in 6 patients, and radiation therapy in 6 patients. Six patients had not received prior chemotherapy or radiation. The treatment consisted of intravenous infusions of 2 formulations of ANP, A10 and AS2-1, and was administered for an average of 20 months. The average dosage of A10 was 10.3 g/kg/d and of AS2-1 was 0.38 g/kg/d. Complete response was accomplished in 23%, partial response in 8%, stable disease in 31%, and progressive disease in 38% of cases. Six patients (46%) survived more than 5 years from initiation of ANP; 5 were not treated earlier with radiation therapy or chemotherapy. The serious side effects included single occurrences of fever, granulocytopenia, and anemia. The study is ongoing and accruing additional patients. The percentage of patients' response is lower than for standard treatment of favorable PNET, but long-term survival in poor-risk cases and reduced toxicity makes ANP promising for very young children, patients at high risk of complication of standard therapy, and patients with recurrent tumors.

Brainstem glioma carries the worst prognosis of all malignancies of the brain. Most patients with brainstem glioma fail standard radiation therapy and chemotherapy and do not survive longer than 2 years. Treatment is even more challenging when an inoperable tumor is of high-grade pathology (HBSG). The objective of this report is to summarize the outcome of patients with HBSG treated with antineoplastons in 4 phase 2 trials. Patients: The following group of 18 patients was evaluable: 4 patients with glioblastomas and 14 patients with anaplastic HBSG. Fourteen patients had diffuse intrinsic tumors. Twelve patients suffered from recurrence, and 6 patients did not have radiation therapy or chemotherapy. Antineoplastons, which consist of antineoplaston A10 (A10I) and AS2-1 injections, were given in escalating doses by intravenous injections. The median duration of antineoplaston administration was 5 months, and the average dosage of A10I was 9.22 g/kg/d and of AS2-1 was 0.31 g/kg/d. Responses were assessed by gadolinium-enhanced magnetic resonance imaging and positron emission tomography. The overall survival at 2 and 5 years was 39% and 22%, respectively, and maximum survival was more than 17 years for a patient with anaplastic astrocytoma and more than 5 years for a patient with glioblastoma. Progression-free survival at 6 months was 39%. Complete response was achieved in 11%, partial response in 11%, stable disease in 39%, and progressive disease in 39% of patients. Antineoplastons were tolerated very well with 1 case of grade 4 toxicity (reversible anemia). Antineoplastons contributed to more than a 5-year survival in recurrent diffuse intrinsic glioblastomas and anaplastic astrocytomas of the brainstem in a small group of patients.

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.

While many cancer patients derive strength from spiritual or religious faith, concern often remains regarding how different patient subgroups and other community members might react to faith-based services when sponsored by a secular health care organization. "A Sacred Gathering for Those Touched by Cancer" was presented in 2 Catholic and 2 Protestant churches. The service included key themes (surrendering fear, peace, hope, community support, and God's love) reinforced by Scripture, music, ritual, and prayer. Patients, clergy, and staff participated. Questionnaires evaluating attendee characteristics, emotional response to the service, and satisfaction with service components were distributed. Attendees (women: 80%; Catholic: 71%; half older than 50 years) returned 450 questionnaires. Most found the service very (83%) or somewhat (14%) helpful. Multivariate regression of perceptions indicated (1) the opinion that the service was helpful was associated with the perception that the service made the respondent feel hopeful (P < .0001), that respondents found inspirational messages important (P = .058), and that the respondent was a current patient (P = .018) and (2) an angry response reported by respondents was associated with current patient status (P = .0044). Men tended to feel less loved by God (P = .012) and people (P = .034) and less hopeful (P = .057) than women did. Men liked music less (P = .048), liked Scripture and prayers concerning community less (P = .040), and found prayer (P = .0035) less important. However, men felt the gatherings were as helpful as women did. Past patients felt less sadness than did others (P = .0084). Increased perceived helpfulness of the service was associated in a multivariate analysis with current patient status, feeling hopeful as a result of the service, increased appreciation of the service's inspirational message, and the perception that the service was not too long. While almost all attendees found the service somewhat or very helpful, distinct preferences and reactions to the service were noted for gender, patient status, and religious affiliation. This evaluation will help tailor future events to better meet the spiritual needs of cancer patients and their loved ones.

In cancer care, there are 2 complementary goals of treatment: eliminating cancer cells and supporting the well-being and healing abilities of the patient. Interactive Guided Imagery(sm)(IGI) can be used to help the patient access inner strengths and resources when high anxiety levels may make that difficult. Three brief cases illustrate the use of IGI to help patients access a "big picture" perspective on their treatment and healing path; to find strength to persevere in their treatment course; and to help make a difficult decision. In all 3 cases, there are multiple personal benefits of the imagery that continued to be of importance throughout the course of each patient's treatment.

Background: High-grade gliomas are the most common and invasive malignant brain tumors in adults, and they are almost universally fatal because of drug resistance and recurrence. In spite of the progress in adjuvant therapy (like temozolomide) and irradiation after surgery, no effective salvage therapy is currently available for relapsed patients. A Korean herbal recipe MSC500 has been reported to have beneficial therapeutic effects in patients with high-grade gliomas who are relapsed or refractory to conventional treatments. But the underlying molecular mechanisms remain unclear. Methods: As Cancer stem cell (CSC) plays a pivotal role in the resistance to conventional cancer therapy, we explored the effects of MSC500 on the CSC-like side population (SP) in GBM8401 human glioblastoma multiforme cells. Results: Compared with the parental cells, the SP cells were more resistant to temozolomide but sensitive to MSC500. The mRNA levels of stemness genes such as Nanog, CD133, and ABCG2 were much higher in the SP cells, and so was E-cadherin, which was reported to correlate with the aggressiveness of glioblastoma multiforme. Treatment with MSC500 decreased the proportion of SP cells and high ALDH activity cells from 1.6% to 0.3% and from 0.9% to 0.1%, respectively, accompanied with suppression of the aforementioned stemness genes and E-cadherin, as well as other CSC markers such as ABCB5, Oct-4, Sox-2, β-catenin, Gli-1, and Notch-1. Conclusion: Our results suggest the potential role of MSC500 as an integrative and complementary therapeutic for advanced or refractory high-grade glioma patients.

Lung and breast cancers are leading causes of cancer death worldwide. Prior exploratory work has shown that patterns of biochemical markers have been found in the exhaled breath of patients with lung and breast cancers that are distinguishable from those of controls. However, chemical analysis of exhaled breath has not shown suitability for individual clinical diagnosis. The authors used a food reward-based method of training 5 ordinary household dogs to distinguish, by scent alone, exhaled breath samples of 55 lung and 31 breast cancer patients from those of 83 healthy controls. A correct indication of cancer samples by the dogs was sitting/lying in front of the sample. A correct response to control samples was to ignore the sample. The authors first trained the dogs in a 3-phase sequential process with gradually increasing levels of challenge. Once trained, the dogs' ability to distinguish cancer patients from controls was then tested using breath samples from subjects not previously encountered by the dogs. The researchers blinded both dog handlers and experimental observers to the identity of breath samples. The diagnostic accuracy data reported were obtained solely from the dogs' sniffing, in double-blinded conditions, of these breath samples obtained from subjects not previously encountered by the dogs during the training period. Among lung cancer patients and controls, overall sensitivity of canine scent detection compared to biopsy-confirmed conventional diagnosis was 0.99 (95% confidence interval [CI], 0.99, 1.00) and overall specificity 0.99 (95% CI, 0.96, 1.00). Among breast cancer patients and controls, sensitivity was 0.88 (95% CI, 0.75, 1.00) and specificity 0.98 (95% CI, 0.90, 0.99). Sensitivity and specificity were remarkably similar across all 4 stages of both diseases. Training was efficient and cancer identification was accurate; in a matter of weeks, ordinary household dogs with only basic behavioral "puppy training" were trained to accurately distinguish breath samples of lung and breast cancer patients from those of controls. This pilot work using canine scent detection demonstrates the validity of using a biological system to examine exhaled breath in the diagnostic identification of lung and breast cancers. Future work should closely examine the chemistry of exhaled breath to identify which chemical compounds can most accurately identify the presence of cancer.

Despite the shift to patient-centered care in recent years, many clinical studies continue to reinforce the traditional researcher/subject relationship. In contrast, action research engages study participants in a collaborative relationship with researchers. To review the benefits of adding a participatory component to an existing study with respect to (1) engaging participants in the research process to clarify and validate qualitative findings, (2) engaging participants in the change process to develop potential solutions for improving integrative cancer services, and (3) giving voice to the concerns of patients using complementary and alternative medicine. Focus groups were used to clarify concepts arising from patient interviews and to provide a forum for participants to develop recommendations and facilitate dissemination. Our approach empowered patients by involving them in the research and in developing solutions for how health care providers, policy makers, and researchers can enhance an integrative approach to cancer care.