Integrative Cancer Therapies

Published by SAGE Publications
Online ISSN: 1534-7354
Publications
Article
Furano-1,2-naphthoquinone (FNQ), a biologically active component of Avicennia marina, has been demonstrated to display anticancer activity. FNQ exerted cytotoxicity with the G(2)/M cell cycle arrest and apoptosis in Ca9-22 cells. FNQ-induced G(2)/M arrest was correlated with a marked decrease in the expression levels of cyclin A and cyclin B, and their activating partner cyclin-dependent kinases (CDK) 1 and 2 with concomitant induction of p27. FNQ-induced apoptosis was accompanied by Bax and Bad upregulation, and the downregulation of Bcl-2, Bcl-X(L), Mcl-1, and X-linked inhibitor of apoptosis (XIAP), resulting in cytochrome C release and sequential activation of caspase-9 and caspase-3. Mechanistic studies showed that FNQ suppressed Src phosphorylation, PI3K, and Akt activation in Ca9-22 cells. Moreover, the Src inhibitor PP2 reduced the phosphorylation of Src and activation of PI3K/Akt, which was comparable with FNQ treatment. The combined treatment of FNQ with PP2 enhanced the cell cycle arrest and apoptosis and also led to the downregulation of Bcl-X(L), Mcl-1, XIAP, cyclin A, cyclin B, CDK1, and CDK2 and upregulation of p27, Bax, and Bad. These findings suggest that FNQ-mediated cytotoxicity of Ca9-22 cells is related with the G(2)/M cell cycle arrest and apoptosis via inactivation of Src and PI3K/Akt-mediated signaling pathways.
 
Article
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 disclosure rates and timeframe of use for four CAM modalities (n=283) in consultation with a CAM practitioner. 
Article
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.
 
Article
The aim of this study was to determine the effects of (125)I seeds on prostate carcinoma (PC3) cells. The relative biological effectiveness of (125)I seeds on PC3 cells with respect to (60)Co gamma rays was 1.4. Both 4 Gy of (60)Co gamma ray and (125)I seed irradiation increased the percentage of cells in G(2) phase, but there was no significant difference between these 2 types of radiation. Significantly, (125)I seeds induced higher apoptotic rates of PC3 cells compared with (60)Co gamma ray irradiation. Furthermore, Bcl-2 expression, but not caspase-3 activity, in PC3 cells was downregulated after irradiation with (125)I seed or (60)Co gamma rays.
 
Article
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.
 
Article
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.
 
Article
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.
 
Article
Taiwan National Health Insurance (NHI) provides Western medicine and Chinese medicine (CM). This study aims to explore the trends of CM use among prostate cancer patients under NHI. Claims of CM outpatient services from 1996 to 2008 were obtained from NHI Research Database. CM visits of prostate cancer patients were identified. Claims with diagnosis code of prostate cancer were defined as cancer-specific visits. Among 78 323 prostate cancer patients identified during 1996-2008, there were 30 383 (38.8%) CM users and 327 063 CM outpatient visits. The prevalence of CM use in each cross-sectional year increased slightly from 24.9% to 25.6%. Most CM visits (92.7%) were non-cancer-specific. There were greater increases in the proportion of cancer-specific CM visits (from 2.3% to 10.6%) and high-utility CM users (from 3.1% to 19.7%). Most CM services were provided by private clinics (68.1% to 79.2%). The most frequently used CM therapies were Chinese herbal medicine (72.8% to 78.8%), followed by acupuncture/traumatology manipulative therapies (28.1% to 36.8%). Total CM cost increased from $122 247 to $825 454. The average cost per CM visit increased from $14.0 to $19.6. The annual cost per CM user increased from $88.0 to $134.4. Copayment accounted for 6.6% to 11.7%. There was a trend of increased CM use among prostate cancer patients under NHI. Although prostate cancer patients used CM mostly for noncancer diseases, CM visits for prostate cancer increased remarkably. The utilization patterns of CM visits for cancer and for noncancer diseases were distinctly different.
 
Article
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.
 
Article
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 gamma-radiation in the HepG2 cell line.
 
Article
Objective: The adverse effects of 5-fluorouracil (5-FU) are well recognized. Fuzheng-Yiliu granule (FYG) is capable of enhancing the immune function and suppressing tumor growth. In the present study, the authors evaluated if FYG could synergize with low-dose 5-FU in inhibiting tumor growth. Methods: Hepatoma 22 (H22) tumor-bearing mice were treated with FYG (18 g/kg, ig), 5-FU (10 mg/kg, ip), or 5-FU plus FYG for 5 days. The relative tumor proliferation rates, tumor weight and apoptosis of tumor tissue were measured. White blood cell (WBC) and lymphocyte (LY) were counted. Interleukin-2 (IL-2) and tumor necrosis factor (TNF-a) in the serum were measured. Results: FYG alone had antitumor effect. Combination of 5-FU and FYG produced a more potent antitumor effect and caused more marked apoptosis in tumor tissue (compared with vehicle, P < 0.01; compared with 5-FU or FYG, P < 0.05). Mice treated with 5-FU plus FYG had higher thymus index (P < 0.05) compared with the vehicle group. The numbers of both WBC and LY were decreased by 5-FU (compared with vehicle, P < 0.01), which was significantly reversed after FYG was administered (5-FU + FYG vs 5-FU, P < 0.01 and P < 0.05). Mice receiving FYG alone or FYG plus 5-FU had higher serum levels of TNF-a (P <0.01) compared with the vehicle. Conclusions: Traditional Chinese medical herbs capable of strengthening the body's vital energy have great potential to be used as an adjuvant therapy for cancer patients who cannot tolerate the adverse effects of chemotherapy.
 
Article
In China, traditional Chinese herbal medicine (TCHM) has been widely used for pancreatic cancer. This retrospective, matched case-control study aimed to assess factors affecting the survival time of patients with pancreatic cancer. From 2004 to 2012, a total of 411 patients with pathologically confirmed pancreatic cancer were enrolled, and 272 patients were matched and divided into TCHM and non-TCHM groups (control group) based on received TCHM or not. The match was according to gender, age of onset, radiotherapy, and chemotherapy. Both groups received comprehensive treatments, the TCHM group simultaneously received the TCHM spleen-invigorating compound for more than 3 months. The Cox model was used for prognostic factor analysis and the Kaplan-Meier method for estimating median overall survival (OS) and disease-free survival (DFS). In 130 patients with advanced pancreatic cancer, COX analysis showed the Karnofsky Performance Scale (KPS; P = .000), radiotherapy (P = .003), and TCHM (P = .001) were independent prognostic factors for OS, with median OS of 12.7 and 9.9 months in TCHM and non-TCHM groups, respectively (hazard ratio [HR] = 0.520; 95% confidence interval [CI] = 0.353-0.766; P = .033). In 142 patients undergoing radical surgery, KPS (P = .000) and TCHM (P = .000) were independent prognostic factors for OS and DFS, median OS was 23.8 and 12.4 months in TCHM and non-TCHM groups, respectively (HR = 0.373; 95% CI = 0.251-0.554; P = .000), and the median DFS was 21.5 and 10.2 months in TCHM and non-TCHM groups, respectively (HR = 0.352; 95% CI = 0.237-0.522; P = .000). KPS was an important prognostic factor of pancreatic cancer. Spleen-invigorating compounds could have an effect on improving the prognosis of pancreatic cancer patients. © The Author(s) 2015.
 
Article
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.
 
Article
The chloroform extract of Physalis minima produced a significant growth inhibition against human T-47D breast carcinoma cells as compared with other extracts with an EC(50) value of 3.8 microg/mL. An analysis of cell death mechanisms indicated that the extract elicited an apoptotic cell death. mRNA expression analysis revealed the coregulation of apoptotic genes, that is, c-myc , p53, and caspase-3. The c-myc was significantly induced by the chloroform extract at the earlier phase of treatment, followed by p53 and caspase-3. Biochemical assay and ultrastructural observation displayed typical apoptotic features in the treated cells, including DNA fragmentation, blebbing and convolution of cell membrane, clumping and margination of chromatin, and production of membrane-bound apoptotic bodies. The presence of different stages of apoptotic cell death and phosphatidylserine externalization were further reconfirmed by annexin V and propidium iodide staining. Thus, the results from this study strongly suggest that the chloroform extract of P. minima induced apoptotic cell death via p53-, caspase-3-, and c-myc-dependent pathways.
 
Laboratory Values for Patient S.M. During Treatment for Metastatic Breast Cancer Date and Treatment Event 
(A) Pretreatment contrast-enhanced computed tomography scan of the abdomen. There are numerous bilobar hypodense liver tumors consistent with metastatic breast cancer. (B) Positron emission tomography scan before radioembolization. Note the large amount of FDG uptake within the liver (arrow). This is due to the metabolically active tumor. 
(A) Right hepatic angiogram in the early arterial phase. (B) Delayed arterial phase angiogram with parenchymal staining. Note the multiple tumor blushes (arrows). 
Planar nuclear medicine shunt study. Technetium 99 macroaggregated albumin was injected into the hepatic artery and becomes lodged at the precapillary level of the liver (arrow). Intratumoral shunts occur within the liver, and a certain amount of radioactivity will become trapped within the lung capillaries (outlined). The patient can be treated with a SIR-Spheres radioembolization if the shunt ratio is less than 20%. S.M.'s was 6%. 
Article
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.
 
Article
Mucuna macrocarpa Wallich (Leguminosae) is believed to hold blood circulation activating effects, and has been used as a folk remedy in Southeast Asia for the treatment of various hematologic and circulatory-related ailments. The objective of this study was to investigate whether crude methanolic extract of M macrocarpa (CMEMM) possessed antileukemic effects on HL-60, human leukemia cells. CMEMM was prepared from dried stems of this plant, and its apoptosis-inducing effects were investigated using HL-60 cells in vitro and in vivo. With treatment of 25 to 75 μg/mL CMEMM, the in vitro antiproliferative effect on HL-60 cells increased in a dose- and time-dependent manner during the 72-hour treatment period. The concentration of CMEMM that exhibited a 50% growth inhibition (IC(50)) for 72-hour exposure was 36.4 μg/mL. Apoptosis triggered by CMEMM in HL-60 cells was confirmed by the following observations: ( a) characteristic apoptotic nuclear fragmentation, (b) dose-dependent accumulation of sub-G(1) phase in cell cycle analyses, (c) increased percentages of annexin V-positive apoptotic cells, and (d) dose-dependent elevation of active caspase-3. Furthermore, an in vivo tumor growth suppression effect by CMEMM (500 mg/kg/d intraperitoneally) was observed in mouse xenografts. The results suggest that CMEMM exerts antileukemic effects via an apoptotic pathway in HL-60 cells, and could be a candidate for developing antileukemic agents in the future.
 
Article
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.
 
Article
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.
 
Article
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.
 
Article
Objective: The chemopreventive potential of (+)-catechin-rich extract of Acacia catechu (L.f.) Willd. heartwood (AQCE) was evaluated against human breast adenocarcinoma cell line (MCF-7) and 7,12-dimethylbenz[a]anthracene (DMBA)-induced mammary carcinoma in Balb/c mice. Methods: Cell cytotoxicity was investigated using different colorimetric assays. Apoptosis was observed using diphenylamine assay and fluorescent microscopy. AQCE was further evaluated for antitumor activity against DMBA-induced mammary carcinoma. The levels of tumor markers and oxidative stress were measured. Furthermore, level of transcription factors was measured by enzyme-linked immunosorbent assay. Results: The results showed that administration of AQCE showed a dose-dependent growth inhibition response and DNA fragmentation in MCF-7 cells. Tumor multiplicity was significantly decreased to 42.91% with AQCE when compared with DMBA-treated animals. The levels of tumor markers such as total sialic acid and lipid-associated sialic acid were substantially increased after DMBA treatment. However, AQCE treatment restored tumor markers level. AQCE also significantly reduced elevated levels of nitrite and malondialdehyde in DMBA-treated animals. Additionally, AQCE also increased the activities of antioxidant enzymes, viz., catalase, superoxide dismutase, total thiol, reduced glutathione, protein thiol, glutathione peroxidase, glutathione reductase, and glutathione-S-transferase in the mammary tissue and liver mitochondria of DMBA-administered animals. Significant increase in the protein levels of p53, c-jun, and p65 were observed in DMBA-treated mice, whereas less expression was observed in AQCE-treated animals. Eventually, AQCE also significantly improved body weight and maintained the mammary tissue architecture in normal range. Conclusions: The present data strongly suggest that anticancer potentiality of (+)-catechin-rich AQCE may be attributable to its ability to positively modulate tumor markers as well as the antioxidant system that could decompose the peroxides and, thereby, offer a protection against lipid peroxidation and linked to the expression of transcription factors during DMBA-induced mammary carcinoma.
 
Effects of DAS Extracts Against Sarcoma-180 Ascites in BALB/c Mice. 1 
In vitro cytotoxic activity of DAS-A001 against various human cancer cells lines in the sulforhodamine B (SRB) assay. Estimated IC 50 values are NA, 12, 13, >100, >100, and 100 µg/mL for A549, HCT-116, PC3, A431, HeLa, and THP-1 respectively. NA implies not active (A); DAS-A002 against various human cancer cells lines in the SRB assay. Estimated IC 50 values are NA, <5, 13, >100, >100, and 65 µg/mL for A549, HCT-116, PC3, A431, HeLa, and THP-1 respectively (B); DAS-A003 against various human cancer cells lines in the SRB assay. Estimated IC 50 values are NA, NA, NA, >100, >100, and <5 µg/mL for A549, HCT-116, PC3, A431, HeLa, and THP-1, respectively (C); DAS-A004 against various human cancer cells lines in the SRB assay. Estimated IC 50 values are NA, <5, 17, >100, >100, and 87 µg/mL for A549, HCT-116, PC3, A431, HeLa, and THP-1 respectively (D).  
Effects of DAS-A002 and DAS-A003 Extracts Against Sarcoma-180 Solid Tumor in BALB/c Mice. 1 
Effect of DAS-A002 and DAS-A003 in L1210 Lymphoid Leukemia in CDF1 Mice. a 
Article
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.
 
Article
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.
 
Article
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.
 
Article
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.
 
Article
Objective: Ethanolic extract of Gymnema sylvestre (GS) leaves is used as a potent antidiabetic drug in various systems of alternative medicine, including homeopathy. The present study was aimed at examining if GS also had anticancer potentials, and if it had, to elucidate its possible mechanism of action. Methods: We initially tested possible anticancer potential of GS on A375 cells (human skin melanoma) through MTT assay and determined cytotoxicity levels in A375 and normal liver cells; we then thoroughly studied its apoptotic effects on A375 cells through protocols such as Hoechst 33258, H2DCFDA, and rhodamine 123 staining and conducted ELISA for cytochrome c, caspase 3, and PARP activity levels; we determined the mRNA level expression of cytochrome c, caspase 3, Bcl2, Bax, PARP, ICAD, and EGFR signaling genes through semiquantitative reverse transcriptase polymerase chain reaction and conducted Western blot analysis of caspase 3 and PARP. We also analyzed cell cycle events, determined reactive oxygen species accumulation, measured annexin V-FITC/PI and rhodamine 123 intensity by flow cytometry. Results: Compared with both normal liver cells and drug-untreated A375, the mortality of GS-treated A375 cells increased in a dose-dependent manner. Additionally, GS induced nuclear DNA fragmentation and showed an increased level of mRNA expression of apoptotic signal related genes cytochrome c, caspase 3, PARP, Bax, and reduced expression level of ICAD, EGFR, and the anti-apoptotic gene Bcl2. Conclusion: Overall results indicate GS to have significant anticancer effect on A375 cells apart from its reported antidiabetic effect, indicating possibility of its palliative use in patients with symptoms of both the diseases.
 
Article
This study reports the antimigration, anti-invasive effect of glabridin, a flavonoid obtained from licorice, in human non-small cell lung cancer A549 cells. Glabridin exhibited effective inhibition of cell metastasis by decreasing cancer cell migration and invasion of A549 cells. In addition, glabridin also decreased A549-mediated angiogenesis. Further investigation revealed that glabridin's inhibition of cancer angiogenesis was also evident in a nude mice model. Blockade of A549 cells migration was associated with an increase of ανβ3 integrin proteosome degradation. Glabridin also decreased the active forms of FAK and Src, and enhanced levels of inactivated phosphorylated Src (Tyr 527), decreasing the interaction of FAK and Src. Inhibition of the FAK/Src complex by glabridin also blocked Akt activation, resulting in reduced activation of RhoA and myosin light chain phosphorylation. This study demonstrates that glabridin may be a novel anticancer agent for the treatment of lung cancer in 3 different ways: inhibition of migration, invasion, and angiogenesis.
 
Article
Tumor metastasis is the most important cause of cancer death and various treatment strategies have targeted at preventing the occurrence of metastasis. Phyllanthus urinaria L is a popular folk medicine and has several proven biological properties, including antioxidant, antihypertension, and anti-inflammatory. This study provides molecular evidence associated with the antimetastatic effects of P urinaria L extracts (PUE), which contained polyphenols including gallic acid, methyl gallate, epicatechin, epigallocatechin-3-gallate, gallocatechin-3-gallate, rutin, epicatechin-3-gallate, and naringin, by showing a marked inhibition on the invasion (P < .001) and migration (P < .001) of highly metastatic A549 and Lewis lung carcinoma (LLC) cells. To further investigate the precise involvement of PUE in tumor metastasis, A549 and LLC cells were treated with PUE at various concentrations and results from zymography and Western blotting showed that a PUE treatment may decrease the expressions of matrix metalloproteinase-2 (MMP-2; P < .001), MMP-9 (P < .001), urokinase plasminogen activator (P < .001), and their endogenous inhibitors, that is, tissue inhibitor of metalloproteinase-2 and plasminogen activator inhibitor-1, in a concentration-dependent manner. Reverse transcription-polymerase chain reaction and MMP-2 promoter luciferase analysis (P < .001) revealed that PUE inhibits the transcription of MMP-2 mRNA. PUE also exerted an inhibitory effect on the DNA-binding activity and the nuclear translocation of NF-κB and AP-1. Furthermore, the inhibitory effects of PUE on the metastasis and growth of LLC cells in vivo were proven. These results indicate that PUE could be applied to be a potential antimetastatic agent.
 
Article
The metastasis of lung cancer is the most prevalent cause of patient death. Various treatment strategies have targeted the prevention of the occurrence of metastasis. The epithelial-mesenchymal transition (EMT) in lung cancer cells is considered a prerequisite to acquire the invasive/migratory phenotype and to subsequently achieve metastasis. However, the effects of RUBUS IDAEU: on cancer invasion and the EMT of the human lung carcinoma remain unclear. In this article, we test the hypothesis that R IDAEU: ethyl acetate (RIAE) possesses an antimetastatic effect and reverses the EMT potential of human lung A549 cells. We extract the raspberry R IDAEU: with methanol (RIME), chloroform (RICE), ethyl acetate (RIAE), : -butanol (RIBE), and water (RIWE). The RIAE treatment obviously inhibits the invasive ( : < .001), motility ( : < .001), spreading, and migratory potential ( : < .001) of highly metastatic human lung cancer A549 cells. The zymography and promoter luciferase analysis reveals that RIAE decreases the proteinase and transcription activities of MMP-2 and u-PA. Molecular analyses show that RIAE increases the E-cadherin level that is mainly localized at the cellular membrane. This result was also verified through confocal analyses. RIAE also induces the upregulation of an epithelial marker, such as α-catenin, and decreases mesenchymal markers, such as snail-1 and N-cadherin, that promote cell invasion and metastasis. RIAE inhibits MMP-2 and u-PA by attenuating the NF-κB and p-Akt expression. The inhibition of RIAE on the growth of A549 cells in vivo was also verified using a cancer cell xenograft nude mice model. Our results show the anti-invasive/antitumor effects of RIAE and associated mechanisms, which suggest that RIAE should be further tested in clinically relevant models to exploit its potential benefits against metastatic lung cancer cells.
 
Article
. In recent years, the incidence of lung cancer, as well as the mortality rate from this disease, has increased. Moreover, because of acquired drug resistance and adverse side effects, the effectiveness of current therapeutics used for the treatment of lung cancer has decreased significantly. Chinese medicine has been shown to have significant antitumor effects and is increasingly being used for the treatment of cancer. However, as the mechanisms of action for many Chinese medicines are undefined, the application of Chinese medicine for the treatment of cancer is limited. The formula tested has been used clinically by the China National Traditional Chinese Medicine Master, Professor Zhonging Zhou for treatment of cancer. In this article, we examine the efficacy of Ke formula in the treatment of non-small cell lung cancer and elucidate its mechanism of action. . A Balb/c nude mouse xenograft model using A549 cells was previously established. The mice were randomly divided into normal, mock, Ke, cisplatin (DDP), and co-formulated (Ke + DDP) groups. After 15 days of drug administration, the animals were sacrificed, body weight and tumor volume were recorded, and the tumor-inhibiting rate was calculated. A cancer pathway finder polymerase chain reaction array was used to monitor the expression of 88 genes in tumor tissue samples. The potential antiproliferation mechanism was also investigated by Western blot analysis. . Ke formula minimized chemotherapy-related weight loss in tumor-bearing mice without exhibiting distinct toxicity. Ke formula also inhibited tumor growth, which was associated with the downregulation of genes in the PI3K/AKT, MAPK, and WNT/β-catenin pathways. The results from Western blot analyses further indicated that Ke blocked the cell cycle progression at the G1/S phase and induced apoptosis mainly via the PI3K/AKT pathway. . Ke formula inhibits tumor growth in an A549 xenograft mouse model with no obvious side effects. Moreover, Ke exhibits synergistic antitumor effects when combined with DDP. The mechanism of action of Ke is to induce cell cycle arrest and apoptosis by suppressing the PI3K/AKT pathway. Further research will be required to determine the mechanism of action behind the synergistic effect of Ke and DDP.
 
Article
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.
 
CONSORT diagram. 
Tai Chi Chih Movements. 
Baseline Characteristics of Participants by Study Arm. a HEC (n = 31) TCC (n = 32) P Value 
Participants' percentage of class attendance by study arms. 
Health-Related Quality of Life SF-36v1 Postintervention Adjusted Means for Subscales and Summary Scores. a HEC (n = 25), M adj (SE) TCC (n = 29), M adj (SE) P Value 
Article
Objective: The purpose of this randomized controlled trial (RCT) was to examine the feasibility and acceptability of a Tai Chi Chih (TCC) intervention in senior female cancer survivors with physical functioning limitations, and its effects on health-related quality of life (QOL). Design: This was a two-armed, parallel group, RCT with 12-weeks of Tai Chi Chih or Health Education Control. Methods: Sixty-three senior (M age = 67 years, SD = 7.15) female cancer survivors (83% breast cancer, stages I-III) with physical functioning limitations (SF-12 Health Survey role-physical & physical functioning subscales) were randomized to 12-weeks of TCC or Health Education control (HEC). Primary outcomes were feasibility and acceptability. Secondary outcomes included health-related QOL (SF-36 Health Survey), and participants' qualitative feedback on the intervention. Results: Retention (TCC = 91%; HEC = 81%) and class attendance (TCC = 79%; HEC = 83%) rates, and satisfaction levels for both study arms were high, but did not significantly differ from one another. At one-week post-intervention, none of the SF-36 scores differed between the TCC and HEC groups. Within-group analyses revealed significant improvements in the mental component summary score in TCC (p = 0.01), but not in HEC. Qualitative analyses indicated that the TCC group felt they received mental and physical benefits, whereas HEC group reported on social support benefits and information received. Conclusion: The TCC intervention was found to be a feasible and acceptable modality for senior female cancer survivors. Future, larger definitive trials are needed to clarify TCC dosage effects on QOL in this vulnerable population.
 
Article
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.
 
Article
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.
 
Article
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.
 
Sequential Phases of Dog Training and Testing 
Article
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.
 
Article
Previous cytotoxic (anticancer) evaluations of Elephantopus mollis were mainly focused on its elephantopin derivatives neglecting the combined effect of the phytochemicals in its traditionally used extracts. In this study, the cytotoxic mechanism of its extracts was investigated using methylene blue assay. The cytotoxic screening results revealed the ethyl acetate extract as the most potent extract by displaying prominent dose-dependent and time-dependent growth inhibitions in human liver carcinoma HepG2 cells with the lowest EC(50) value of 9.38 ± 0.43 µg/mL after 72 hours of treatment. Acute exposure of the HepG2 cells to the ethyl acetate extract produced a significant regulation of caspase-3 with the peak expression at 8 hours of treatment (P < .05). DNA fragmentation indicated by DeadEnd Apoptosis Detection System-labeled nuclei cells confirmed that the extract induced apoptotic cell death through caspase-3-dependent pathway in HepG2 cells.
 
Article
Introduction. Visceral pain is one of the most important pains caused by cancer or other diseases, and most of the medications may lead to tolerance, addiction, and toxic side effects. Hua-Jian-Ba-Du Ointment (HJBDO), which is a commonly used conjugate based on traditional Chinese medicine theory, has been effective against visceral pain. Here, we verify the efficacy and underlying mechanism of HJBDO in an acetic-acid induced visceral pain model. Methods. Mice were subjected to acetic acid with or without HJBDO. Hua-Jian-Ba-Du Ointment at low (7.5 mL/kg•d), moderate (15 mL/kg•d), and high (30 mL/kg•d) dosages was applied on the abdomen, 3 times per day for 3 days. The acetic acid writhing test was used to evaluate antinociception. Interleukin-2 (IL-2) in serum, tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and prostaglandin E2 (PGE2) in peritoneal fluid were detected by ELISA. 5-hydroxytryptamine (5-HT), norepinephrine (NE), dopamine (DA), and β-endorphin (β-EP) were examined by high performance liquid chromatography and radioimmunoassay, respectively. N-methyl-D-aspartic acid receptor (NMDAR1) and c-fos expressions in both rostral ventromedial medulla (RVM) and spinal dorsal horn were determined by western blot. Results. Hua-Jian-Ba-Du Ointment at 3 dosage levels produced dose-dependent antinociception and shortened the latent time. Hua-Jian-Ba-Du Ointment at high or moderate dosage inhibited the release of TNF-α, IL-6, and PGE2, as well as increased the release of IL-2. Hua-Jian-Ba-Du Ointment could also increase NE and 5-HT contents and decrease the NE content. No effect of HJBDO at 3 dosages on the DA system was detected. Furthermore, HJBDO could suppress the expressions of NMDAR and c-fos in both RVM and spinal dorsal horn. Conclusion. Our results exhibited the analgesic effect of HJBDO on visceral pain in mice, and this effect might be mediated by the regulation of inflammation and neurotransmitters. © The Author(s) 2015.
 
Article
Hepatocellular carcinoma (HCC) is one of the most malignant human tumors and one of the risk factors is its highly metastatic property. Coptidis Rhizoma aqueous extract (CRAE) is able to suppress the migration and invasion of HCC cells, MHCC97-L, and F-actin reorganization and Rho signaling inhibition is involved. CRAE was prepared and analyzed by high-performance liquid chromatography combined with mass spectrometry. The cytotoxicity and antimigration action of CRAE on MHCC97-L cells were evaluated; Immunofluorescence and immunoblotting were used to investigate the proposed mechanism of CRAE action. Chemical analysis reveals that the active components in CRAE are berberine and berberine-like alkaloids. CRAE exhibits a significant inhibitory effect on MHCC97-L cell migration as indicated by wound-healing and invasion-chamber assays. No significant alteration of matrix metalloproteinases and urokinase-type plasminogen activator (uPA) expression were observed in MHCC97-L cells exposed to CRAE. Reduction of F-actin polymerization and damage to cytoskeleton network in MHCC97-L cells were observed after CRAE treatment. Furthermore, it was found that CRAE significantly downregulated the Rho/ROCK signaling pathway. These results indicate that CRAE may act as a Rho/ROCK signaling inhibitor to suppress MHCC97-L cell migration in vitro and suggested that total alkaloids in Coptidis Rhizoma may be a potential agent for suppressing liver cancer invasion.
 
Article
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.
 
Article
Silymarin, the active extract from milk thistle, has been extensively used in patients with liver disease of different etiology. Although silymarin is a complex of 7 flavonolignans and polyphenols, silibinin is usually regarded as the most active component. In vitro and in vivo studies indicate that silymarin and silibinin protect the liver from oxidative stress and sustained inflammatory processes, mainly driven by Reactive Oxygen Species (ROS) and secondary cytokines. Oxidative stress and inflammation are also involved in cellular damage of many other tissues and their role in the development and toxic reactions in patients receiving cancer therapies is established. The protective effects of silymarin and silibinin, demonstrated in various tissues, suggest a clinical application in cancer patients as an adjunct to established therapies, to prevent or reduce their toxicity. Here we discuss the possible mechanism of the protective action of silymarin and silibinin, focusing on cancer therapies as agents causing cellular damage.
 
Article
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)-gamma. 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.
 
Article
There is an increasing body of data showing that activated cancer therapy--the synergistic effect of "preloaded" molecules and a tuned energy source to produce cytopathogenic moieties--is a promising new modality for cancer treatment. The key activated therapies are photodynamic therapy (PDT), which involves the synergy between light and photosensitizer molecules, and ultrasound activated therapy (USAT; also referred to as sonodynamic therapy), which involves the synergy between ultrasound and sonosensitizer molecules. PDT is a well-known activated therapy with roots dating back to 1900. However, minimal data exist on USAT. One reason is the lack of suitable sonosensitizers for clinical USAT use. The authors present both LC(50) toxicity and cancer cell cytotoxicity studies on 2 dual activation agents. These compounds function as both sonosensitizers and photosensitizers, and are referred to as SonneLux agents, designated SF1 and SF2. The sensitizers are derived from chlorophyll and are metal centered porphyrins known to specifically accumulate in hyperproliferating tissue. LC(50) studies on both SF1 and SF2 as determined in zebra fish reveal that both are essentially nontoxic to zebra fish. In the worst case, 5% zebra fish death is noted at the maximum soluble concentration of the sensitizer. In the cytotoxicity studies, melanoma cell line WM-266-4, derived from a metastatic site of a malignant melanoma, was tested against SF1 and SF2. Both sensitizer systems showed marked efficacy in the destruction of the implanted melanoma cells. They show great promise for clinical use in the future.
 
Ability of antiestrogens to block stimulatory effect of alcohol-extracted American ginseng (alc-GE) on MCF-7 cells maintained in low-estrogen conditions. Cells were treated every 2 days for a total of 6 days with 0.05 mg/mL alc-GE and/or 0.1 µM 4-hydroxytamoxifen (Tam) or 1.0 nM ICI 182,780. Media with 0.1% ethanol served as vehicle control. Data are displayed as total cell number ± SEM for 3 independent experiments. *P < .05 when compared to controls.
Article
Ginseng root extracts and the biologically active ginsenosides have been shown to inhibit proliferation of human cancer cell lines, including breast cancer. However, there are conflicting data that suggest that ginseng extracts (GEs) may or may not have estrogenic action, which might be contraindicated in individuals with estrogen-dependent cancers. The current study was designed to address the hypothesis that the extraction method of American ginseng (Panax quinquefolium) root will dictate its ability to produce an estrogenic response using the estrogen receptor (ER)-positive MCF-7 human breast cancer cell model. MCF-7 cells were treated with a wide concentration range of either methanol-(alc-GE) or water-extracted (w-GE) ginseng root for 6 days. Cells were grown in media containing either normal or charcoal-stripped fetal calf serum to limit exposure to exogenous estrogen. Thus, an increase in MCF-7 cell proliferation by GE indicated potential estrogenicity. This was confirmed by blocking GE-induced MCF-7 cell proliferation with ER antagonists ICI 182,780 (1 nM) and 4-hydroxytamoxifen (0.1 microM). Furthermore, the ability of GE to bind ERalpha or ERbeta and stimulate estrogen-responsive genes was examined. Alc-GE, but not w-GE, was able to increase MCF-7 cell proliferation at low concentrations (5-100 microg/mL) when cells were maintained under low-estrogen conditions. The stimulatory effect of alc-GE on MCF-7 cell proliferation was blocked by the ER antagonists ICI 182,780 or 4-hydroxyta-moxifen. At higher concentrations of GE, both extracts inhibited MCF-7 and ER-negative MDA-MB-231 cell proliferation regardless of media conditions. Binding assays demonstrated that alc-GE, but not w-GE, was able to bind ERalpha and ERbeta. Alc-GE (50 microg/mL) also induced an approximate 2.5-fold increase in expression of the estrogen-responsive pS2 gene, as well as progesterone receptor (PgR) gene expression, whereas w-GE was without effect. These data indicate that low concentrations of alc-GE, but not w-GE, elicit estrogenic effects, as evidenced by increased MCF-7 cell proliferation, in a manner antagonized by ER antagonists, interactions of alc-GE with estrogen receptors, and increased expression of estrogen-responsive genes by alc-GE. Thus, discrepant results between different laboratories may be due to the type of GE being analyzed for estrogenic activity.
 
Induction of apoptosis by Phyllanthus amarus: Dalton's lymphoma ascites (DLA) cells were treated with indicated concentrations of P.amarus for 48 hours. Figure 1A shows untreated DLA cells after 48 hours. Figure 1B shows P.amarus-treated cells with apoptotic changes (pointed arrows). 
Effect of Phyllanthus amarus (500 µg/mL) on in Vitro Proliferation of Cell Lines (MTT Assay) 
Induction of DNA fragmentation by Phyllanthus amarus extract in Dalton's lymphoma ascites (DLA) cells. Lane 1, molecular weight marker; lane 2, DNA isolated from untreated DLA cells; lane 3, DNA isolated from DLA cells treated with P.amarus 200 µg/mL; lane 4, DNA isolated from DLA cells treated with P.amarus 100 µg/mL. 
Effect of administration of P.amarus on Bcl-2 expression in DLA cells: Lane 1: Molecular weight marker (100bp); Lane 2: Treated with P.amarus showing no expression of BCl-2; Lane 3: Control DLA cells showing expression of Bcl-2 (235bp); Lane 4: Positive control for Bcl-2 (235bp); Lane 5: GAPDH (557bp). 
Effect of administration of P.amarus on caspase 3 and p53 expression in DLA cells: Lane 1: Molecular weight marker (100bp); Lane 2: Control DLA cells without any expression of caspase 3; Lane 3: Treated with P.amarus showing expression of caspase 3 (414bp); Lane 4: Positive control for caspase 3 (414bp); Lane 5: Control DLA cells without any expression of p53; Lane 6: Treated with P.amarus without any expression of p53; Lane 7: Positive control for p53 (205bp); Lane 8: GAPDH (557bp). 
Article
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 microg/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.
 
Article
Nomilin is a triterpenoid present in common edible citrus fruits with putative anticancer properties. In this study, the authors investigated the antimetastatic potential of nomilin and its possible mechanism of action. Metastasis was induced in C57BL/6 mice through the lateral tail vein using highly metastatic B16F-10 melanoma cells. Administration of nomilin inhibited tumor nodule formation in the lungs (68%) and markedly increased the survival rate of the metastatic tumor-bearing animals. These results correlated with the biochemical parameters and histopathological analysis. Nomilin showed an inhibition of tumor cell invasion and activation of matrix metalloproteinases. Treatment with nomilin induced apoptotic response, characterized by an increase in the sub-G1 fraction of cells with chromatin condensation and membrane blebbing, a typical ladder of DNA fragmentation, and detection of apoptotic cells by TUNEL assay. Nomilin treatment also exhibited a downregulated Bcl-2 and cyclin-D1 expression and upregulated p53, Bax, caspase-9, caspase-3, p21, and p27 gene expression in B16F-10 cells. Proinflammatory cytokine production and gene expression were found to be downregulated in nomilin-treated cells. The study also reveals that nomilin could inhibit the activation and nuclear translocation of antiapoptotic transcription factors such as nuclear factor (NF)-κB, CREB, and ATF-2 in B16F-10 cells.
 
Top-cited authors
Keith I Block
  • Block Center for Integrative Cancer Treatment , Skokie, Illinois, USA
Marja Verhoef
  • The University of Calgary
Dugald Seely
  • The Canadian College of Naturopathic Medicine
Michael Mcculloch
  • Pine Street Foundation
Janice Post-White
  • University of Minnesota Twin Cities