Rutin attenuates intestinal toxicity induced by Methotrexate linked with anti-oxidative and anti-inflammatory effects
Jitendra Kumar Rawat,
Shubhini A Saraf and
Abstract Background Methotrexate (MTX) is recognized as an anti-metabolite in cancer chemotherapy and is associated with various toxicities assigned to inflammation and oxidative stress. Rutin has been reported to have significant anti-inflammatory, antioxidant along with antiulcer properties. The present study was undertaken to corroborate the effect of rutin against MTX induced intestinal toxicity in experimental animals.
Method Six groups of rats (n = 6) were dosed with normal saline (3 ml/kg,i.p.); MTX (2.5 mg/kg,i.p.); rutin (50 and 100 mg/kg,i.p.); rutin + MTX (50 mg/kg + 2.5 mg/kg,i.p.); rutin + MTX (100 mg/kg + 2.5 mg/kg,i.p.) for seven consecutive days and sacrificed on eighth day. The intestinal contents were scrutinized physiologically (pH, total acidity, free acidity, CMDI), biochemically (TBARS, protein carbonyl, SOD, catalase and GSH) and for immunoregulatory cytokines (IL-2, IL-4 and IL-10).
Results and Discussion The administration of rutin demonstrated significant protection against intestinal lesions damaged by MTX. The treatment with rutin elicited noticeable inhibition of free acidity (26.20 %), total acidity (22.05 %) and CMDI (1.16 %) in the experimental animals similar to control. In MTX treated toxic group, the levels of oxidative markers and immunoregulatory cytokines significantly increased in comparison to control, which was subsequently restored after rutin treatment. Rutin also demonstrated 75.63, 81.00 and 80.43 % inhibition of cyclooxygenase-1 and 2, and 15-lipoxygenase respectively.
Conclusion The positive modulation of MTX toxicity could be attributed to the free radical scavenging and anti-inflammatory (dual inhibition of arachidonic acid pathways) potential of rutin.
Panax notoginseng saponins suppress radiation-induced osteoporosis by regulating bone formation and resorption. Abstract Background: While radiation-based therapies are effective for treating numerous malignancies, such treatments can also induce osteoporosis.
Purpose: We assessed the antiosteoporotic properties of total saponins extracted from the leaves of Panax notoginseng (LPNS) in a mouse model of radiation-induced osteoporosis and in vitro.
Study design/methods: The bone mineral densities, the marker of bone formation and resorption, and inflammatory factors were measured in vivo. Cell proliferation and differentiation were detected in vitro.
Results: The results showed that bone mineral densities in irradiated mice administered LPNS were significantly increased compared to those in irradiated mice which had not received LPNS. LPNS attenuated the inflammation caused by irradiation, and significantly increased blood serum AKP activity, the mRNA levels of RUNX2 and osteoprotegerin, and the numbers of CFU-Fs formed by bone marrow cells collected from irradiated mice. In contrast, LPNS decreased the numbers of osteoclast precursor cells ([CD117.sup.+]/[RANKL.sup.+] cells and [CD71.sup.+]/[CD115.sup.+] cells) and the mRNA levels of TRAP and ATP6L These results suggest that LPNS functions as a negative regulator of bone resorption. In vitro assays showed that LPNS promoted the differentiation of bone marrow mesenchymal stem cells and mononuclear cells into osteoblasts and osteoclasts, respectively, but had no effect on osteoclast activation.
Conclusion: These results demonstrate that LPNS has significant antiosteoporotic activity, which may warrant further investigations concerning its therapeutic effects in treating radiation-induced osteoporosis.
Source : Phytomedicine: International Journal of Phytotherapy + Phytopharmacology Link to Full Article
The Hepatoprotective Effect of Haoqin Qingdan Decoction against Liver Injury Induced by a Chemotherapeutic Drug Cyclophosphamide Xiaojiang Li, Baole Li, and Yingjie Jia
Department of Oncology, First Teaching Hospital of Tianjin University of Traditional Chinese Medicine, 314 An Shan Xi Dao, Nan Kai District, Tianjin 300193, China
Abstract Haoqin Qingdan decoction (HQQD), a modern Chinese formula, has been widely used in Eastern Asia. Our study focuses on the hepatoprotective effect of HQQD against cyclophosphamide-induced hepatotoxicity. S180, a kind of ascites tumor cells, was used to establish S180-bearing mice, followed by the injection of cyclophosphamide (CP, 80 mg/kg) every other day for 5 times. HQQD was used intragastrically at the dose of 80 g/kg, 40 g/kg, and 20 g/kg twice a day for 12 days. HL-7702 hepatic cell line was incubated with HQQD-medicated serum. Then we detected the effects of HQQD on (i) tumor suppression; (ii) morphological examination; (iii) SOD, MDA, GSH, ALT, and AST; (iv) cleaved caspase-3 expression and (v) cellular viability. CP caused dramatic elevations of AST, ALT, and MDA, while HQQD notably attenuated these elevations. SOD and GSH were notably increased, which were efficiently attenuated by HQQD. CP injection significantly increased apoptosis by increasing cleaved caspase-3 expression, which was obviously inhibited by HQQD, accompanied by the improvement of cells viability. Histopathological examinations supported the above findings. Therefore, HQQD may protect liver tissue through attenuating oxidative stress and the caspase-3-dependent intrinsic apoptosis induced by CP, which suggests the potentially therapeutic effect of HQQD in the use of alkylating agent for cancer chemotherapy.
"Coffee plus Honey" versus "topical steroid" in the treatment of Chemotherapy-induced Oral mucositis: a randomised controlled trial Mohammad Ali Raeessi, Neda Raeessi, Yunes Panahi, Homa Gharaie, Seyyed Masoud Davoudi, Alireza Saadat, Ali Akbar Karimi Zarchi, Fereshteh Raeessi, Seyyed Mostafa Ahmadi and Hamidreza Jalallian
Abstract Background Oral mucositis is one of the common complications of cancer chemotherapy and about 40% of the patients who take chemotherapy protocols, experience this irritating problem. The purpose of this study was to draw comparison between the therapeutic effects of our treatment modalities (topical steroid, honey, honey plus coffee) in patients suffering from oral mucositis.
Methods This was a double blinded randomised clinical trial of a total of 75 eligible adult participants which they randomly fell into three treatment groups. For all the participants a syrup-like solution was prepared. Each 600 grams of the product consisted of "20 eight-mg Betamethasone solution ampoules" in the Steroid (S) group, "300 grams of honey plus 20 grams of instant coffee" in the Honey plus Coffee (HC) group, and "300 grams of honey" for the Honey (H) group. The participants were told to sip 10 ml of the prescribed product, and then swallow it every three hours for one week. Severity of lesions was clinically evaluated before the treatment and also one week after the initiation of the intervention. This study adhered to the principles of the Declaration of Helsinki and guidelines of Good Clinical Practice.
Results This study showed that all three treatment regimens reduce the severity of lesions. The best reduction in severity was achieved in HC group. H group and S group took the second and third places. In other words, honey plus coffee regimen was the most effective modality for the treatment of oral mucositis.
Conclusion Oral mucositis can be successfully treated by a combination of honey and coffee as an alternative medicine in a short time. Further investigations are warranted in this field
Purpose Intestinal mucositis is a common adverse effect in patients undergoing radiotherapy and constitutes a treatment-limiting condition. Since no agents are yet known that can adequately guard against its development, the search continues to find safe and effective measures. The present study was intended to investigate whether the herbal preparation, STW 5, could offer a potentially effective agent in this respect.
Methods Intestinal mucositis was induced in rats by exposing them to whole body gamma-irradiation (6Gy). Rats were treated orally with STW 5 (5 or 10ml/kg) for five days before and two days after irradiation. One day later, rats were sacrificed and segments of small intestine were examined histologically. Intestinal homogenates and serum samples were used to assess relevant parameters for apoptosis and different markers for inflammation and oxidative stress.
Results Exposure to radiation produced dose-dependent extents of intestinal injury associated with apoptotic changes with high radiation levels. Apoptosis was associated with an increase in cytosolic calcium, depletion of mitochondrial cytochrome c, B-cell lymphoma-2 and complex I. Oxidative stress parameters (reduced glutathione, thiobarbituric acid reactive substance and total nitrate/nitrite) were deranged. Inflammation markers (tumor necrosis factor and myeloperoxidase) and indices of intestinal damage (serum diamine oxidase) were increased. STW 5 protected to a large extent against histological changes and counteracted the deranged parameters.
Conclusion The findings provide experimental evidence for the potential beneficial use of STW5 in protecting against the development of radiation-induced intestinal mucositis and associated changes in tissue biomarkers.
Effects of Spiritual Healing for Women Undergoing Long-Term Hormone Therapy for Breast Cancer: A Qualitative Investigation Fiona Barlow, PhD, MBACP(Accred),1 Jan Walker, PhD,2 and George Lewith, MD, FRCP3
1Health Experiences Research Group, University of Oxford, Oxford, United Kingdom 2School of Nursing and Midwifery, University of Southampton, Southampton, United Kingdom. 3School of Medicine, University of Southampton, Southampton, United Kingdom.
Abstract Background: Spiritual Healing is widely available and used, but is a neglected area for research and its biologic and psychologic mechanisms are not understood. The side-effects of long-term hormonal therapy for breast cancer are onerous and have been reported to lead to “drug holidays” that could diminish the long-term treatment benefits. It was investigated whether Spiritual Healing could support patients with breast cancer undergoing this treatment.
Methods: The qualitative observation study took place in a specialist research facility in a general hospital. Spiritual Healing was provided by 4 healers registered with the National Federation of Spiritual Healers. Twelve (12) patients with breast cancer undergoing long-term hormone treatment and who found the effects onerous, self-referred themselves and were given ten weekly sessions of approximately 40 minutes each. Data collected included participant's daily records, direct observations noted by healers, the researcher's field diary and a one-to-one semi-structured interview.
Findings:The positive effects of Spiritual Healing included alleviation of the physical side-effects of their treatment, increased energy levels, enhanced well-being, emotional relaxation, and re-engagement with precancer activities. Although 1 participant admitted considering a drug holiday prior to joining the study, none of the participants felt tempted to stop their hormonal treatments while receiving Spiritual Healing.
Conclusions: These qualitative findings indicate that Spiritual Healing has the potential to support patients with breast cancer in the maintenance of their long-term orthodox treatments. Further research is needed to test Spiritual Healing as a cost-effective complementary therapy, for those undergoing long-term cancer treatments
A randomized, controlled clinical trial of the homeopathic medication TRAUMEEL S in the treatment of chemotherapy-induced stomatitis in children undergoing stem cell transplantation. Oberbaum M, Yaniv I, Ben-Gal Y, Stein J, Ben-Zvi N, Freedman LS, Branski D.
The Institute of Research on Complementary Medicine, The Center of Integrated Complementary Medicine, Shaare Zedek Medical Center, P.O. Box 3235, Jerusalem 91031, Israel. email@example.com
Abstract BACKGROUND: Stomatitis is a common consequence of chemotherapy and a condition for which there is little effective treatment. Although the management of patients with other chemotherapy-related toxicities has improved in recent years, the incidence of stomatitis is increasing because of more intensive treatment and is often a dose limiting factor in chemotherapy. The authors assessed the efficacy of a homeopathic remedy, TRAUMEEL S(R), in the management of chemotherapy-induced stomatitis in children undergoing bone marrow transplantation.
METHODS: A randomized, placebo-controlled, double-blind clinical trial was conducted in 32 patients ages 3-25 years who had undergone allogeneic (16 patients) or autologous (16 patients) stem cell transplantation. Of the 30 evaluable patients, 15 were assigned placebo, and 15 were assigned TRAUMEEL S both as a mouth rinse, administered five times daily from 2 days after transplantation for a minimum of 14 days, or until at least 2 days after all signs of stomatitis were absent. Stomatitis scores were evaluated according to the World Health Organization grading system for mucositis.
RESULTS: A total of five patients (33%) in the TRAUMEEL S treatment group did not develop stomatitis compared with only one patient (7%) in the placebo group. Stomatitis worsened in only 7 patients (47%) in the TRAUMEEL S treatment group compared with 14 patients (93%) in the placebo group. The mean area under the curve stomatitis scores were 10.4 in the TRAUMEEL S treatment group and 24.3 in the placebo group. This difference was statistically significant (P < 0.01).
CONCLUSIONS: This study indicates that TRAUMEEL S may reduce significantly the severity and duration of chemotherapy-induced stomatitis in children undergoing bone marrow transplantation.
Topical Yunnan Baiyao administration as an adjunctive therapy for bleeding complications in adolescents with advanced cancer
E. J. Ladas,
J. B. Karlik,
D. H. Ndao,
K. M. Kelly
Purpose Yunnan Baiyao (White Medicine from Yunnan, YNB) is a Chinese herbal medicinal powder used to stop bleeding and improve circulation in traumatic injuries. We describe the use of YNB in adolescents with cancer as an adjunct to uncontrolled bleeding in the palliative care setting.
Methods Through a retrospective chart review of all patients receiving integrative medicine consultations at the Integrative Therapies Program at Columbia University from January 1, 2007 to January 31, 2012, we describe the outcome of patients treated with YNB for management of uncontrolled bleeding.
Results Four patients were identified who received topical YNB for uncontrolled bleeding; patients included two males and two females with diagnoses of solid tumors (n = 3) and Burkitt’s lymphoma (n = 1). Mean age was 15.5 years (range 15–17). Fifty percent had life-threatening bleeding from the tumor site and 50 % experienced uncontrollable epistaxis. All patients received preceding therapy with packed red blood cells and platelet transfusions, topical thrombin, and oral aminocaproic acid. Two patients used YNB in the inpatient setting, and all four patients used YNB as outpatients. In all patients, bleeding control improved with the addition of YNB to conventional hemostatic interventions. Two patients using YNB in their home reported control of bleeding episodes. There were no adverse events reported.
Conclusions YNB may be an efficacious agent for uncontrolled bleeding in conjunction with conventional hemostatic agents in adolescents with advanced cancer. It is well accepted by patients. YNB may be especially valuable in the outpatient setting to prevent the recurrence of hemorrhage
Source : Support Care Cancer (2012) 20:3379–3383 DOI 10.1007/s00520-012-1598-1 Download Full Article Below
Probiotic factors partially prevent changes to caspases 3 and 7 activation and transepithelial electrical resistance in a model of 5-fluorouracil-induced epithelial cell damage Luca D. Prisciandaro & Mark S. Geier & Ann E. Chua & Ross N. Butler & Adrian G. Cummins & Guy R. Sander & Gordon S. Howarth
Abstract The potential efficacy of a probiotic-based preventative strategy against intestinal mucositis has yet to be investigated in detail. We evaluated supernatants (SN) from Escherichia coli Nissle 1917 (EcN) and Lactobacillus rhamnosus GG (LGG) for their capacity to prevent 5- fluorouracil (5-FU)-induced damage to intestinal epithelial cells. A 5-day study was performed. IEC-6 cells were treated daily from days 0 to 3, with 1 mL of PBS (untreated control), de Man Rogosa Sharpe (MRS) broth, tryptone soy roth (TSB), LGG SN, or EcN SN. With the exception of the untreated control cells, all groups were treated with 5-FU (5 μM) for 24 h at day 3. Transepithelial electrical resistance (TEER) was determined on days 3, 4, and 5, while activation of caspases 3 and 7 was determined on days 4 and 5 to assess apoptosis. Pretreatment with LGG SN increased TEER (p<0.05) compared to controls at day 3. 5-FU administration reduced TEER compared to untreated cells on days 4 and 5. Pretreatment with MRS, LGG SN, TSB, and EcN SN partially prevented the decrease in TEER induced by 5-FU on day 4, while EcN SN also improved TEER compared to its TSB vehicle control. These differences were also observed at day 5, along with significant improvements in TEER in cells treated with LGG and EcN SN compared to healthy controls. 5-FU increased caspase activity on days 4 and 5 compared to controls. At day 4, cells pretreated with MRS, TSB, LGG SN, or EcN SN all displayed reduced caspase activity compared to 5-FU controls, while both SN groups had significantly lower caspase activity than their respective vehicle controls. Caspase activity in cells pretreated with MRS, LGG SN, and EcN SN was also reduced at day 5, compared to 5-FU controls. We conclude that pretreatment with selected probiotic SN could prevent or inhibit enterocyte apoptosis and loss of intestinal barrier function induced by 5-FU, potentially forming the basis of a preventative treatment modality for mucositis.
Source : Support Care Cancer (2012) 20:3205–3210 DOI 10.1007/s00520-012-1446-3 Download Full Article below
Uncaria tomentosa—Adjuvant Treatment for Breast Cancer: Clinical Trial
Maria do Carmo Santos Araújo,1,2 Iria Luiza Farias,1,2 Jessie Gutierres,1 Sergio L. Dalmora,3,4 Nélia Flores,2 Julia Farias,1 Ivana de Cruz,5 Juarez Chiesa,2 Vera Maria Morsch,1 and Maria Rosa Chitolina Schetinger1
1Department of Chemistry, Federal University of Santa Maria, Avenida Roraima, Predio18, 97105-900 Santa Maria, Rs, Brazil 2Santa Maria University Hospital, Federal University of Santa Maria, Avenida Roraima, Predio18, 97105-900 Santa Maria, Rs, Brazil 3Department of Biology, Federal University of Santa Maria, Avenida Roraima, Predio18, 97105-900 Santa Maria, Rs, Brazil 4Department of Industrial Pharmacy, Federal University of Santa Maria, Avenida Roraima, Predio18, 97105-900 Santa Maria, Rs, Brazil 5Department of Morphology, Federal University of Santa Maria, Avenida Roraima, Predio18, 97105-900 Santa Maria, Rs, Brazil
Abstract Breast cancer is the most frequent neoplasm affecting women worldwide. Some of the recommended treatments involve chemotherapy whose toxic effects include leukopenia and neutropenia. This study assessed the effectiveness of Uncaria tomentosa (Ut) in reducing the adverse effects of chemotherapy through a randomized clinical trial. Patients with Invasive Ductal Carcinoma—Stage II, who underwent a treatment regimen known as FAC (Fluorouracil, Doxorubicin, Cyclophosphamide), were divided into two groups: the UtCa received chemotherapy plus 300 mg dry Ut extract per day and the Ca group that only received chemotherapy and served as the control experiment. Blood samples were collected before each one of the six chemotherapy cycles and blood counts, immunological parameters, antioxidant enzymes, and oxidative stress were analyzed. Uncaria tomentosa reduced the neutropenia caused by chemotherapy and was also able to restore cellular DNA damage. We concluded that Ut is an effective adjuvant treatment for breast cancer.
Source : Evidence-Based Complementary and Alternative Medicine Volume 2012 (2012) Link to Full Article
Guarana (Paullinia cupana) Improves Fatigue in Breast Cancer Patients Undergoing Systemic Chemotherapy Maira Paschoin de Oliveira Campos, MD,1 Rachel Riechelmann, MD, PhD,2 Lourdes Conceic¸a˜o Martins,1 Benjamin J. Hassan, MD,3 Fernanda Branco Assunc¸a˜o Casa,4 and Auro Del Giglio, MD, PhD2,5
Abstract Background: In patients with breast cancer (BC) undergoing systemic chemotherapy, cancer-related fatigue (CRF) is a common problem that can negatively impact quality of life. Guarana (Paullinia cupana) is a plant native to the Amazon basin that has been used as a stimulant since pre-Columbian times.
Objective: The purpose of this study was to evaluate the effectiveness of guarana extract on fatigue, sleep quality, anxiety, depression symptoms, and menopause in a group of BC chemotherapy patients.Patients and methods: Patients with progressive fatigue after their first cycle of chemotherapy were randomized to receive either guarana 50mg by mouth twice daily (32 patients) or placebo (43 patients) for 21 days. After a 7-day washout period, patients were crossed over to the opposite experimental arm. All patients were evaluated on days 1, 21, and 49. The primary endpoint was the Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) questionnaire score, and secondary endpoints were the results of the Functional Assessment of Chronic Illness Therapy-Endocrine Symptoms (FACT-ES), Brief Fatigue Inventory (BFI), Pittsburg Sleep Quality Index, Chalder Fatigue Scale, and Hospital Anxiety and Depression Scale.
Results: Guarana significantly improved the FACIT-F, FACT-ES, and BFI global scores compared to placebo on days 21 and 49 ( p<0.01). The Chalder Scale improved significantly on day 21 ( p<0.01) but not on day 49 ( p¼0.27). Guarana did not produce any Common Terminology Criteria for Adverse Events grades 2, 3, or 4 toxicities and did not worsen sleep quality or cause anxiety or depression.
Conclusions: Guarana is an effective, inexpensive, and nontoxic alternative for the short-term treatment of fatigue in BC patients receiving systemic chemotherapy. Further studies are needed to confirm these results and to evaluate their generalizability to chronic CRF and to other types of cancer.
Source : THE JOURNAL OF ALTERNATIVE AND COMPLEMENTARY MEDICINE Volume 17, Number 6, 2011, pp. 505–512 Link to Full Article
Triphala, an Ayurvedic Rasayana Drug, Protects Mice Against Radiation-Induced Lethality by Free-Radical Scavenging GANESH CHANDRA JAGETIA, Ph.D., KRISHNA J. MALAGI, M.D. (Ayu), MANJESHWAR SHRINATH BALIGA, Ph.D., PONEMONE VENKATESH, M.SC. (Medical), and ROSI REDDY VERUVA, M.Pharm.
ABSTRACT The effects of 10 mg/kg of triphala extract (TE) was studied on radiation-induced sickness and mortality in mice exposed to 7–12 Gray (Gy) of -irradiation. Treatment of mice with triphala once daily for 5 consecutive days before irradiation delayed the onset of mortality and reduced the symptoms of radiation sickness when compared with the non-drug double distilled water treated irradiated controls (DDW). Triphala provided protection against both gastrointestinal and hemopoetic death. However, animals of both the TE irradiation and DDW irradiation groups did not survive up to 30 days post-irradiation beyond 11 Gy irradiation. The LD50/30 was found to be 8.6 Gy for the DDW irradiation group and 9.9 Gy for TE irradiation group. The administration of triphala resulted in an increase in the radiation tolerance by 1.4 Gy, and the dose reduction factor was found to be 1.15. To understand the mechanism of action of triphala, the free radical scavenging activity of the drug was evaluated. Triphala was found to scavenge •OH, O2• 2,2-azinobis(3-ethylbenzthiazoline-6-sulfonate) diammonium salt (ABTS)• and NO• radicals in a dose dependent manner.
Conclusion From our study it is clear that TE provided protection against radiation-induced sickness and mortality in mice and its free radical scavenging and antioxidant activities may beresponsible for the observed radioprotection. Further experimental studies are planned to explore how TE may modulate the radiation-induced damage in radiation fractionation, for its utility in cancer treatment and its effect on cancer growth.
NB - Composition of the drug Triphala (tri three, phala fruits) is a mixture of fruits of three plants: Terminalia chebula Retz. (Family Combretaceae), Terminalia bellerica (Gaertn.) Roxb. (Family Combretaceae), and Phyllanthus emblica (Linn) or Emblica officinalis (Gaertn.) (Euphorbiaceae) in powdered form in equal proportions (1:1:1).
Source : THE JOURNAL OF ALTERNATIVE AND COMPLEMENTARY MEDICINE Volume 10, Number 6, 2004, pp. 971–978 Link to Full Article
Docosahexaenoic acid: A natural powerful adjuvant that improves efficacy for anticancer treatment with no adverse effects. Siddiqui RA, Harvey KA, Xu Z, Bammerlin EM, Walker C, Altenburg JD
Cellular Biochemistry Laboratory, Indiana University Health, Indiana University School of Medicine, Indianapolis, IN 46202, USA; Department of Medicine, Indiana University School of Medicine, Indianapolis, IN 46202, USA. firstname.lastname@example.org.
Abstract Epidemiological studies have linked fish oil consumption to a decreased incidence of cancer. The anticancer effects of fish oil are mostly attributed to its content of omega-3 fatty acids: eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). However, DHA, because of its unique effect of altering membrane composition, is often regarded as the major omega-3 fatty acid involved in anticancer activity. Although use of DHA as an anticancer drug to prevent or treat human cancer in clinical settings has not yet been well established, recent studies suggest that DHA can be very effective as an adjuvant with other anticancer agents. In this article, we present studies that show the role of DHA in improving anticancer drug efficacy. Several in vitro and animal studies suggest that combining DHA with other anticancer agents often improves efficacy of anticancer drugs and also reduces therapy-associated side effects. Incorporation of DHA in cellular membranes improves drug uptake, whereas increased lipid peroxidation is another mechanism for DHA-mediated enhanced efficacy of anticancer drugs. In addition, several intracellular targets including cyclooxygenase-2, nuclear factor kappa B, peroxisome proliferator-activated receptor gamma, mitogen-activated protein kinase, AKT, and BCL-2/BAX are found to play an important role in DHA-mediated additive or synergistic interaction with anticancer drugs. The data suggest that DHA is a safe, natural compound that can greatly improve the anticancer properties of anticancer drugs. Use of DHA with anticancer treatments provides an avenue to therapeutic improvement that involves less risk or side effects for patients and reduced regulatory burden for implementation.
Enhancement of the Response of B16F1 Melanoma to Fractionated Radiotherapy and Prolongation of Survival by Withaferin A and/or Hyperthermia Guruprasad Kalthur, PhD1, and Uma Devi Pathirissery, PhD2
Abstract Withaferin A (WA), isolated from Indian medicinal plant Withania somnifera has weak antitumor and radiosensitizing property. The present investigation was planned to evaluate the tumor sensitizing effect of WA with or without local hyperthermia on the response of B16F1 melanoma to fractionated and acute radiotherapy. C57BL mice bearing tumors of 100 ± 10mm3 were treated with fractionated radiotherapy (RT, 2Gy x 5 days/week, 4 weeks), withaferin A (15mg/kg, i.p., 5 days/week, 3 weeks), local hyperthermia (HT, 43°C once a week, 3 weeks) and their combinations, or acute RT (40Gy), WA (40mg/kg), HT (43°C, 30min) and their combinations. Treatment response was studied by tumor regression, growth delay and animal survival. Acute RT+HT produced 50% partial response which increased to 62.5% with combination of WA. In fractionated regimen, trimodality combination resulted in 100% PR. Acute RT+HT and WA+RT produced similar increase in growth delay (GD) compared to RT alone which further increased in trimodality treatment. Fractionated WA+RT+HT for 3 weeks produced a higher GD and survival than all other treatments. In conclusion, WA is a better radiosensitizer than HT in fractionated regimen and the response of radioresistant tumors like melanoma can be significantly enhanced by combining nontoxic doses of WA with fractionated RT, with or without HT, allowing decrease in radiation dose.
Bojungikki-Tang for Cancer-Related Fatigue: A Pilot Randomized Clinical Trial Jong Soo Jeong, MD (KMD), MS1, Bong Ha Ryu, MD (KMD), PhD1, Jin Sung Kim, MD (KMD), PhD1, Jae Woo Park, MD (KMD), PhD1, Won Cheol Choi, MD (KMD), PhD1, and Seong Woo Yoon, MD (KMD), PhD1
Abstract Background: Bojungikki-tang (Bu-Zhong-Yi-Qi-Tang in Chinese or Hochu-ekki-to in Japanese) is a widely used herbal prescription in traditional medicine in China, Japan, and Korea. The aim of this study was to investigate the effectiveness of Bojungikki-tang for cancer-related fatigue.
Methods: A total of 40 patients with cancer-related fatigue were randomized into an experimental or a waiting list control group. Patients in the experimental group were treated with Bojungikki-tang (TJ-41) and patients in the waiting list group remained without any intervention for 2 weeks.
Results: The experimental group showed statistically significant improvements in fatigue level assessed by the Visual Analogue Scale of Global Fatigue (VAS-F) measuring the severity of fatigue (experimental vs control: -1.1 ± 2.1 vs 0.1 ± 0.9, P < .05) and results of Functional Assessment of Cancer Therapy–General (FACT-G), Functional Assessment of Cancer Therapy–Fatigue (FACT-F), and Trial Outcome Index–Fatigue (TOI-F) also showed significant improvements (FACT-G, 3.7 ± 9.9 vs -2.4 ± 9.5, P < .05; FACT-F,8.0 ± 13.6 vs -2.2 ± 14.1, P < .05; TOI-F, 6.5 ± 9.2 vs -0.5 ± 10.9, P < .05).
Conclusions: The results of this study indicate that Bojungikki-tang may have beneficial effects on cancer-related fatigue and quality of lives in cancer patients. More rigorous trials are needed to confirm the efficacy of Bojungikki-tang.
Cardioprotective effects of Curcuma longa L. extracts against doxorubicin-induced cardiotoxicity in rats Eman M. El-Sayed1, Amal S. Abd El-azeem1, Abeer A. Afify1, Manal H. Shabana2 and Hanaa H. Ahmed3
1Food Sciences and Nutrition Department, National Research Centre, Dokki, Cairo, Egypt. 2Phytochemistry and Plant Systematic Department, National Research Centre, Dokki, Cairo, Egypt. 3Hormones Department, National Research Centre, Dokki, Cairo, Egypt.
Abstract This study was designed to investigate the possible mechanisms whereby Curcuma longa could protect against cardiotoxicity induced by doxorubicin. Administration of doxorubicin (15 mg/kg i.p.) induced cardiomyopathy manifested by significant elevation in serum creatine kinase MB (Ck-MB) and lactate dehydrogenase (LDH) activities. In addition, cardiotoxicity was further confirmed by significant increase in each of serum and cardiac malondialdehyde (MDA) level, serum iron and nitric oxide concentrations, cardiac calcium level, catalase and glucose-6 phosphate dehydrogenase activities as well as by the noticeable reduction in cardiac total antioxidant capacity, vitamin C levels and blood glutathione (GSH) concentration. Oral administration of Curcuma longa ethanolic or water extract (200 mg/kg) prior to doxorubicin produced a significant protection which was evidenced by significant reduction in mortality, CK-MB and LDH -activities. Moreover, they significantly increased GSH markedly, decreased cardiac calcium, and cardiac and serum MDA. In addition, both extracts significantly reduced serum nitric oxide, increased cardiac ascorbic acid, and ameliorated the antioxidant enzymes activities. In conclusion, Curcuma longa extracts renders resiliency against doxorubicin cardiotoxicity due to their contents of polyphenolic compounds that might serve as novel adjuvant therapy with doxorubicin.
Source : Journal of Medicinal Plants Research Vol. 5(17), pp. 4049-4058, September 2011 Link to Full Article
DIETARY FLAXSEED PREVENTS RADIATION-INDUCED OXIDATIVE LUNG DAMAGE, INFLAMMATION AND FIBROSIS IN A MOUSE MODEL OF THORACIC RADIATION INJURY James C. Lee, M.D.,* Ryan Krochak, B.S.,* Aaron Blouin,* Stathis Kanterakis, B.S.,+ Shampa Chatterjee, Ph.D.,* Evguenia Arguiri, B.S.,* Anil Vachani, M.D.,* Charalambos C. Solomides, M.D.,† Keith A. Cengel, M.D., Ph.D.,‡ and Melpo Christofidou-Solomidou, PhD.**
Department of Medicine, Pulmonary Allergy and Critical Care Division, Philadelphia, PA 19104+ Department of Pharmacology, University of Pennsylvania Medical Center, Philadelphia, PA 19104‡ Radiation Oncology, University of Pennsylvania Medical Center, Philadelphia, PA 191044 †Department of Pathology, Temple University Hospital, Philadelphia, PA 19140
Abstract Flaxseed (FS) has high contents of omega-3 fatty acids and lignans with antioxidant properties. Its use in preventing thoracic X-ray radiation therapy (XRT)-induced pneumonopathy has never been evaluated. We evaluated FS supplementation given to mice given before and post-XRT. FS-derived lignans, known for their direct antioxidant properties, were evaluated in abrogating ROS generation in cultured endothelial cells following gamma radiation exposure. Mice were fed 10% FS or isocaloric control diet for three weeks and given 13.5 Gy thoracic XRT. Lungs were evaluated at 24 hours for markers of radiation-induced injury, three weeks for acute lung damage (lipid peroxidation, lung edema and inflammation), and at four months for late lung damage (inflammation and fibrosis). FS-Lignans blunted ROS generation in vitro, resulting from radiation in a dose-dependent manner. FS-fed mice had reduced expression of lung injury biomarkers (Bax, p21, and TGF-beta1) at 24 hours following XRT and reduced oxidative lung damage as measured by malondialdehyde (MDA) levels at 3 weeks following XRT. In addition, FS-fed mice had decreased lung fibrosis as determined by hydroxyproline content and decreased inflammatory cell influx into lungs at 4 months post XRT. Importantly, when Lewis Lung carcinoma cells were injected systemically in mice, FS dietary supplementation did not appear to protect lung tumors from responding to thoracic XRT. Dietary FS is protective against pulmonary fibrosis, inflammation and oxidative lung damage in a murine model. Moreover, in this model, tumor radioprotection was not observed. FS lignans exhibited potent radiation-induced ROS scavenging action. Taken together, these data suggest that dietary flaxseed may be clinically useful as an agent to increase the therapeutic index of thoracic XRT by increasing the radiation tolerance of lung tissues.
Polarity Therapy for Cancer-Related Fatigue in Patients With Breast Cancer Receiving Radiation Therapy: A Randomized Controlled Pilot Study
Karen M. Mustian, PhD, MPH,1 Joseph A. Roscoe, PhD,1 Oxana G. Palesh, PhD, MPH,1 Lisa K. Sprod, PhD,1 Charles E. Heckler, PhD,1 Luke J. Peppone, PhD,1 Kenneth Y. Usuki, MD,1 Marilyn N. Ling, MD,1 Ralph A. Brasacchio, MD,1 and Gary R. Morrow, PhD, MS1 University of Rochester, Rochester, NY, USA
Abstract Background Cancer-related fatigue (CRF) is the most frequently reported side effect of cancer and its treatment. In previous research, Polarity Therapy (PT), an energy therapy, was shown to reduce CRF in patients receiving radiation. This study reports on a small randomized clinical trial designed to collect preliminary data on the efficacy of PT compared with an active control (massage) and passive control (standard care) for CRF among cancer patients receiving radiation therapy.MethodsForty-five women undergoing radiation therapy for breast cancer were randomized to I of 3 weekly treatment conditions. Patients received standard clinical care, 3 modified massages, or 3 PT treatments. CRF and healthrelated quality of life (HRQL) were assessed during baseline and the 3 intervention weeks
.Results TResults show CRF ratings were reduced after PT. The effect sizes for PT versus modified massage and versus standard care were small when using the primary measure of CRF (Brief Fatigue Inventory) and large when using the secondary measure of CRF (Daily CRF Diaries).The effect size was medium when assessing the benefit of PT on maintaining HRQL compared with standard care with very little difference between the PT and modified massage conditions. Patients’ feedback showed that both the modified massage and PT treatments were deemed useful by radiation patients.
Conclusion. The present pilot randomized clinical trial supports previous experimental research showing that PT, a noninvasive and gentle energy therapy, may be effective in controlling CRF. Further confirmatory studies as well as investigations of the possible mechanisms of PT are warranted.
Source : Integr Cancer Ther. 2011 March; 10(1): 27–37. doi: 10.1177/1534735410397044 Link to Full Article
Oral Glutamine Protects against Acute Doxorubicin-Induced Cardiotoxicity of Tumor-Bearing Rats
Valentina K. Todorova 3 , * ,
Yihong Kaufmann 5 ,
Leah Hennings 4 , and
V. Suzanne Klimberg 3 , 4
Abstract Doxorubicin (DOX), a widely used anticancer drug, has a dose-dependent cardiotoxicity, attributed mainly to free radical formation. The cardiomyocyte oxidative stress occurs rapidly after DOX treatment, resulting in harmful modifications to proteins, lipids, and DNA. Previous data showed that oral l-glutamine (Gln) prevented cardiac lipid peroxidation and maintained normal cardiac glutathione (GSH) levels in DOX-treated rats. Our aim in this study was to examine the effect of Gln on DOX-induced cardiac oxidative stress in a tumor-bearing host. Female Fisher344 rats with implanted MatBIII mammary tumors were randomized into 2 groups: a Gln group that received l-Gln (1 g·kg−1·d−1) (n = 10) via a Gln-enriched diet and/or gavage with 50% Gln suspension during the whole experiment and a control group that was fed the same diet formulation without Gln and/or were gavaged with water. All rats received a single injection of 12 mg/kg DOX and were killed 3 d later. GSH levels of hearts, livers, tumors, and blood, as well as cardiac histological alterations, lipid peroxidation, peroxinitrite levels, and caspase-3 activation were determined. Cardiac physiologic alterations were assessed by ultrasound imaging before and 3 d after DOX administration. The Gln supplementation resulted in lower cardiac lipid peroxidation and peroxintrite levels and elevated cardiac catalase enzyme activity and GSH compared with the controls, without affecting those of the tumors. DOX-induced alterations of the echocardiographic parameters were significantly reduced in the Gln-supplemented rats. These data indicate that Gln is able to reduce the oxidative damage of cardiomyocytes that occurs soon after DOX administration and thus protects the heart of a tumor-bearing host from DOX-induced cardiomyopathy.
Dietary flaxseed administered post thoracic radiation treatment improves survival and mitigates radiation-induced pneumonopathy in mice
Melpo Christofidou-Solomidou, Sonia Tyagi, Kay-See Tan, Sarah Hagan, Ralph Pietrofesa, Floyd Dukes, Evguenia Arguiri, Daniel F Heitjan, Charalambos C Solomides, Keith A Cengel Departments of Medicine, Pulmonary, Allergy and Critical Care Division, University of Pennsylvania Medical Center, Philadelphia, PA 19104, USA Biostatistics & Epidemiology, University of Pennsylvania Medical Center, Philadelphia, PA 19104, USA Radiation Oncology, University of Pennsylvania Medical Center, Philadelphia, PA 19104, USA Department of Pathology, Jefferson University Hospital, Philadelphia, PA 19140, USA
Abstract Background: Flaxseed (FS) is a dietary supplement known for its antioxidant and anti-inflammatory properties. Radiation exposure of lung tissues occurs either when given therapeutically to treat intrathoracic malignancies or incidentally, such as in the case of exposure from inhaled radioisotopes released after the detonation of a radiological dispersion devise (RDD). Such exposure is associated with pulmonary inflammation, oxidative tissue damage and irreversible lung fibrosis. We previously reported that dietary FS prevents pneumonopathy in a rodent model of thoracic X-ray radiation therapy (XRT). However, flaxseed’s therapeutic usefulness in mitigating radiation effects post-exposure has never been evaluated.
Methods: We evaluated the effects of a 10%FS or isocaloric control diet given to mice (C57/BL6) in 2 separate experiments (n=15-25 mice/group) on 0, 2, 4, 6 weeks post a single dose 13.5 Gy thoracic XRT and compared it to an established radiation-protective diet given preventively, starting at 3 weeks prior to XRT. Lungs were evaluated four months post-XRT for blood oxygenation levels, inflammation and fibrosis.
Results: Irradiated mice fed a 0%FS diet had a 4-month survival rate of 40% as compared to 70-88% survival in irradiated FS-fed mouse groups. Additionally, all irradiated FS-fed mice had decreased fibrosis compared to those fed 0%FS. Lung OH-Proline content ranged from 96.5±7.1 to 110.2±7.7 μg/ml (Mean ± SEM) in all irradiated FS-fed mouse groups, as compared to 138±10.8 μg/ml for mice on 0%FS. Concomitantly, bronchoalveolar lavage (BAL) protein and weight loss associated with radiation cachexia was significantly decreased in all FS-fed groups. Inflammatory cell influx to lungs also decreased significantly except when FS diet was delayed by 4 and 6 weeks post XRT. All FS-fed mice (irradiated or not), maintained a higher blood oxygenation level as compared to mice on 0%FS. Similarly, multiplex cytokine analysis in the BAL fluid revealed a significant decrease of specific inflammatory cytokines in FS-fed mice.
Conclusions: Dietary FS given post-XRT mitigates radiation effects by decreasing pulmonary fibrosis, inflammation, cytokine secretion and lung damage while enhancing mouse survival. Dietary supplementation of FS may be a useful adjuvant treatment mitigating adverse effects of radiation in individuals exposed to inhaled radioisotopes or incidental radiation.
Review Article: Influence of Viscum album L (European Mistletoe) Extracts on Quality of Life in Cancer Patients: A Systematic Review of Controlled Clinical Studies
Gunver S. Kienie, MD, Helmut Kiene, MD Institute for Applied Epistemology and Medical Methodology, Freiburg, Germany Objective. To evaluate controlled clinical studies on the efficacy and effectiveness of Viscum album for quality of life (QoL) in cancer.
Materials and methods. The authors conducted a search of 7 electronic databases and reference lists and had extensive consultations with experts. They carried out a criteria-based assessment of methodological study quality.
Results. The authors identified 26 randomized controlled trials (RCTs) and 10 non-RCTs that investigated the influence of V album extracts (VAEs) on QoL in malignant diseases; 26 studies assessed patient-reported QoL. Questionnaires were mostly well established and validated. Half of the studies investigated VAEs concomitant with chemotherapy, radiotherapy, or surgery. Some studies were well designed, whereas others had minor or major methodological weaknesses. Among the 26 RCTs, 22 reported a QoL benefit, 3 indicated no difference, and 1 did not report any result. All the non-RCTs reported a QoL benefit. Of the studies with higher methodological quality, most reported a benefit, whereas 1 found no difference. Improvements were mainly in regard to coping, fatigue, sleep, exhaustion, energy, nausea, vomiting, appetite, depression, anxiety, ability to work, and emotional and functional well-being in general and, less consistently, in regard to pain, diarrhea, general performance, and side effects of conventional treatments. VAEs were well tolerated.
Conclusions. VAEs seem to have an impact on QoL and reduction of side effects of conventional therapies (chemotherapy, radiation) in experimental trials as well as in routine daily application. The influence on fatigue especially should be investigated further.
Efficacy of Goshajinkigan for Peripheral Neurotoxicity of Oxaliplatin in Patients with Advanced or Recurrent Colorectal Cancer Toru Kono,1 Noriaki Mamiya,1,2 Naoyuki Chisato,1 Yosiaki Ebisawa,1 Hirotaka Yamazaki,3 Jiro Watari,4 Yasuhiro Yamamoto,5 Shigetaka Suzuki,5 Toshiyuki Asama,1 and Kazunori Kamiya6
1Division of Gastroenterologic and General Surgery, Department of Surgery, Asahikawa Medical University, 2-1 Midorigaoka-higashi, Asahikawa, Hokkaido 078-8510, Japan 2Division of Cancer Chemotherapy Center, Higashiasahikawa Hospital, Asahikawa, Japan 3Department of Surgery, Kushiro City Medical Association Hospital, Kushiro, Japan 4Deptartment of Gastroenterology, Kushiro City Medical Association Hospital, Kushiro, Japan 5Department of Surgery, Kobayashi Hospital, Kitami, Japan 6Department of Surgery, Karasawa Hospital, Asahikawa, Japan
Peripheral neurotoxicity is the major limiting factor for oxaliplatin therapy. Goshajinkigan (GJG), a traditional Japanese herbal medicine, was recently shown to be effective in protecting against the neurotoxicity of taxanes in Japan. We retrospectively investigated the effect of GJG on peripheral neurotoxicity associated with oxaliplatin therapy. Ninety patients with metastatic colorectal cancer that received FOLFOX4 or modified FOLFOX6 therapy were assigned to receive one of the following adjuncts: oral GJG at 7.5 g day−1 (Gr oup , 𝑛 = 11) intravenous supplementation of calcium gluconate and magnesium sulfate (1 g each before and after FOLFOX) (Group B, 𝑛=14) a combined GJG and calcium gluconate and magnesium sulfate therapies (Group C, 𝑛=21), or no concomitant therapy (Group D, 𝑛=44) the incidence of peripheral neurotoxicity was investigated when the cumulative dose of oxaliplatin exceeded 500 mg m−2. When the cumulative dose of oxaliplatin exceeded 500 mg m−2, the incidence of neuropathy (all grades) in Groups A–D was 50.0%, 100%, 78.9%, and 91.7%, respectively. It was lowest in the group that received GJG alone. Concomitant administration of GJG reduced the neurotoxicity of oxaliplatin in patients that received chemotherapy for colorectal cancer.
In recent years, the standard chemotherapy for advanced/recurrent colorectal cancer is a continuous intravenous infusion of 5-fluorouracil (5-FU) combined with either oxaliplatin (FOLFOX, FOLFOX4 or modified FOLFOX6) or irinotecan (FOLFIRI) [1–3]. Acute and persistent peripheral neuropathy is the characteristic of oxaliplatin therapy , and the oxaliplatin dose must be limited to avoid toxicity. The prevalence of peripheral neurotoxicity increases with the total accumulated dose of oxaliplatin, and often interferes with the continuation of FOLFOX therapy . Gamelin et al. [6, 7] reported that administration of calcium gluconate and magnesium sulfate (Ca/Mg) before and after oxaliplatin therapy could alleviate peripheral neurotoxicity. Other similar treatments have been described, including carbamazepine [8–10] or glutathione , but an effective remedy for peripheral neurotoxicity related to oxaliplatin therapy has not yet been established.
Goshajinkigan (GJG) is an extracted traditional Japanese herbal medicine (Kampo) that is mainly used for the improvement of symptoms like numbness, cold sensation and limb pain associated with diabetic neuropathy [12–15]. Moreover, Mamiya et al.  and Shindo et al.  recently reported that peripheral neurotoxicity due to oxaliplatin was relieved by administration of GJG in patients with advanced colorectal cancer that were receiving FOLFOX therapy.
We conducted the present retrospective study to compare the efficacy of GJG with that of Ca/Mg for alleviation of peripheral neurotoxicity in patients with advanced or recurrent colorectal cancer that received either FOLFOX4 therapy or modified FOLFOX6 (mFOLFOX6) therapy at our hospital and affiliated institutions in Japan.
Source : Evidence-Based Complementary and Alternative Medicine Volume 2011 (2011), Article ID 418481, 8 pages doi:10.1093/ecam/nep200 LINK TO FULL ARTICLE
Yoga for Persistent Fatigue in Breast Cancer Survivors: Results of a Pilot Study Julienne E. Bower,1,2,3,4 Deborah Garet,3 and Beth Sternlieb5
1Department of Psychology, UCLA, Los Angeles, CA 90095, USA 2Department of Psychiatry and Biobehavioral Sciences, Geffen School of Medicine, UCLA, Los Angeles, CA 90095, USA 3Cousins Center for Psychoneuroimmunology, Semel Institute, UCLA, Los Angeles, CA 90095, USA 4Division of Cancer Prevention and Control Research, Jonsson Comprehensive Cancer Center, UCLA, Los Angeles, CA 90095, USA 5Pediatric Pain Program, Mattel Children's Hospital, UCLA, Los Angeles, CA 90095, USA
Approximately one-third of breast cancer survivors experiences persistent fatigue for months or years after successful treatment completion. There is a lack of evidence-based treatments for cancer-related fatigue, particularly among cancer survivors. This single-arm pilot study evaluated the feasibility and preliminary efficacy of a yoga intervention for fatigued breast cancer survivors based on the Iyengar tradition. Iyengar yoga prescribes specific poses for individuals with specific medical problems and conditions; this trial emphasized postures believed to be effective for reducing fatigue among breast cancer survivors, including inversions and backbends performed with the support of props. Twelve women were enrolled in the trial, and 11 completed the full 12-week course of treatment. There was a significant improvement in fatigue scores from pre- to post-intervention that was maintained at the 3-month post-intervention followup. Significant improvements were also observed in measures of physical function, depressed mood, and quality of life. These results support the acceptability of this intervention and suggest that it may have beneficial effects on persistent post-treatment fatigue. However, results require replication in a larger randomized controlled trial.
Source Evidence-Based Complementary and Alternative Medicine Volume 2011 (2011), Article ID 623168, 8 pages doi:10.1155/2011/623168 Link to Full Article
Randomized trial of a hypnosis intervention for treatment of hot flashes among breast cancer survivors. Journal of Clinical Oncology
Gary Elkins, Joel Marcus, Vered Stearns, Michelle Perfect, M. Hasan Rajab, Christopher Ruud, Lynne Palamara, Timothy Keith From the Department of Psychology and Neuroscience, Baylor University, Waco; Scott and White Memorial Hospital and Clinic, Department of Psychiatry and Behavioral Sciences, Temple; Cancer Treatment and Research Center, San Antonio; and University of Texas at Austin, TX; University of Arizona, Tucson, AZ; and the Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, MD
Purpose Hot flashes are a significant problem for many breast cancer survivors. Hot flashes can cause discomfort, disrupted sleep, anxiety, and decreased quality of life. A well-tolerated and effective mind-body treatment for hot flashes would be of great value. On the basis of previous case studies, this study was developed to evaluate the effect of a hypnosis intervention for hot flashes.
Patients and Methods Sixty female breast cancer survivors with hot flashes were randomly assigned to receive hypnosis intervention (five weekly sessions) or no treatment. Eligible patients had to have a history of primary breast cancer without evidence of detectable disease and 14 or more weekly hot flashes for at least 1 month. The major outcome measure was a bivariate construct that represented hot flash frequency and hot flash score, which was analyzed by a classic sums and differences comparison. Secondary outcome measures were self-reports of interference of hot flashes on daily activities.
Results Fifty-one randomly assigned women completed the study. By the end of the treatment period, hot flash scores (frequency x average severity) decreased 68% from baseline to end point in the hypnosis arm (P < .001). Significant improvements in self-reported anxiety, depression, interference of hot flashes on daily activities, and sleep were observed for patients who received the hypnosis intervention (P < .005) in comparison to the no treatment control group.
Conclusion Hypnosis appears to reduce perceived hot flashes in breast cancer survivors and may have additional benefits such as reduced anxiety and depression, and improved sleep.
Source Journal of Clinical Oncology, Vol 26, No 31 (November 1), 2008: pp. 5022-5026 LINK TO FULL ARTICLE
Suppression of growth, migration and invasion of highly-metastatic human breast cancer cells by berbamine and its molecular mechanisms of action Shang Wang1 Qian Liu,#1 Ying Zhang,#2 Ke Liu,#1 Pengfei Yu,#1 Kun Liu,1 Jinling Luan,1 Huiying Duan,1 Zhaoqiao Lu,1 Fengfei Wang,3 Erxi Wu,3 Kazumi Yagasaki,4 and Guoying Zhang1 1Laboratory of Molecular Pharmacology, School of Pharmacy, Yantai University, No 30, Qing Quan Lu, Lai Shan Qu, Yantai, Shandong Province 264005, China 2Clinical Medicine, Clinical College of Anhui Medical University, No 15, Feicuilu, Hefei, Anhui Province 230601, China 3Department of Pharmaceutical Sciences, North Dakota State University, Fargo, ND, 58105, USA 4Department of Applied Biological Science, Tokyo Noko University, Saiwai-cho 3-5-8, Fuchu, Tokyo 183-8509, Japan
BACKGROUND Breast cancer is the second leading cause of cancer-related deaths among females in the United States . Its rate in China and other Asian countries is also increasing rapidly [2,3]. To find novel natural compounds with low toxicity and high selectivity for killing cancer cells is an important area in cancer research. To date, chemotherapy has been the most frequently used treatment for breast cancer and other cancers. However, some normal cells are destroyed as well by this method of treatment. Due to their wide range of biological activities and low toxicity in animal models, some natural products have been used as alternative treatments for cancers including breast cancer. Berbamine (BER) is a naturally occurring small-molecule compound from Traditional Chinese Medicine (TCM) Berberis amurensis (xiaoboan). In China, BER has been used to treat the clinical patients with inflammation and various cancers including breast cancer, hepatoma, leukemia for many years. BER is also a clinical drug to treat the patients with low levels of white blood cells, which are caused by chemotherapy and/or radiotherapy. The chemical structure of BER is shown in Fig. Fig.1A.1A. BER-induced apoptosis and growth inhibition of human leukemia HL-60 and K562 cell lines without cytotoxicity to normal hematopoietic cells [4-6]. It induced caspase-3-dependent apoptosis of leukemia NB4 cells via survivin-mediated pathway . BER also caused apoptosis and cell cycle arrest, and led to loss of mitochondrial membrane potential and activated caspase-3 and caspase-9 in human hepatoma cells . However, whether or not BER has inhibitory activities against highly-metastatic human breast cancer cells is unclear. In this study, we investigated the effects of BER on growth, migration and invasion of highly-metastatic human breast cancer cells and its molecular mechanisms of action. We showed that BER inhibited the growth, migration and invasion of the highly-metastatic human breast cancer cells as well as induced the apoptosis in the cancer cells. Such anti-cancer activities of BER involved suppression of Akt and NF-κB signaling and its upstream and downstream targets by reducing expressions of the related proteins and mRNA as well as pro-MMP-9/pro-MMP-2 activation in the cells.
Results In our study, we found that BER inhibits growth of highly-metastatic human breast cancer cell lines MDA-MB-231 and MDA-MB-435S cells dose-dependently and time-dependently. The sera from BER-treated rats suppress the growth of MDA-MB-231 cells. BER shows synergistic effects with some existing anticancer agents such as trichostatin A (TSA, the histone deacetylase inhibitor), celecoxib (the inhibitor of COX-2), and carmofur against the growth of MDA-MB-231 cells. BER also displays the strong activity of inducing apoptosis in both estrogen receptor-negative MDA-MB-231 cells and estrogen receptor-alpha-positive MCF-7 breast cancer cells, but not in normal human mammary epithelial cell line MCF10A. BER down-regulates anti-apoptotic protein Bcl-2 levels and up-regulates pro-apoptotic protein Bax expressions in MDA-MB-231 and MDA-MB-435S cells. BER also has synergistic effects with anticancer agents trichostatin A, celecoxib and/or carmofur on reducing Bcl-2/Bax ratios and VEGF secretions in MDA-MB-231 cells. In addition, BER significantly suppresses cell migration and invasion, as well as decreases pro-MMP-9/pro-MMP-2 activation in breast cancer cells. Furthermore, BER suppresses Akt and nuclear factor κB signaling by reducing the phosphorylation of c-Met and Akt, and inhibiting their downstream targets such as nuclear factor κB p-65, Bcl-2/Bax, osteopontin, VEGF, MMP-9 and MMP-2 on protein and/or mRNA levels in breast cancer cells.
Conclusion Our findings have showed that BER suppresses the growth, migration and invasion in highly-metastatic human breast cancer cells by possibly inhibiting Akt and NF-κB signaling with their upstream target c-Met and downstream targets Bcl-2/Bax, osteopontin, VEGF, MMP-9 and MMP-2. BER has synergistic effects with anticancer agents trichostatin A, celecoxib and carmofur on inhibiting the growth of MDA-MB-231 cells and reducing the ratio of Bcl-2/Bax and/or VEGF expressions in the cancer cells. These findings suggest that BER may have the wide therapeutic and/or adjuvant therapeutic application in the treatment of human breast cancer and other cancers.
Efficacy of Liangxue Jiedu Huoxue Decoction in prevention of radiation pneumonitis: a randomized controlled trial 1. Chun Xiao (Department of Traditional Chinese Medicine, Chinese PLA General Hospital, Beijing 100853, China ) 2. Hui-juan Ding (Department of Traditional Chinese Medicine, Chinese PLA General Hospital, Beijing 100853, China ) 3. Lin-chun Feng (Department of Radiotherapy, Chinese PLA General Hospital, Beijing 100853, China ) 4. Bao-lin Qu (Department of Radiotherapy, Chinese PLA General Hospital, Beijing 100853, China ) 5. Yong-qi Dou (Department of Traditional Chinese Medicine, Chinese PLA General Hospital, Beijing 100853, China
Background: Radiation pneumonitis is one of the most common complications during radiotherapy of thoracic tumors. It impacts the quality of life of the patients and has life-threatening danger. However, there is a lack of drugs for prevention and treatment of this disease. Objective: To evaluate the efficacy of Liangxue Jiedu Huoxue Decoction, a compound traditional Chinese herbal medicine, in prevention of radiation pneumonitis. Design, setting, participants and interventions: A prospective randomized clinical study was conducted. A total of 100 patients diagnosed with lung cancer from Department of Radiotherapy, Chinese PLA General Hospital, who were planning to receive radiotherapy, were randomly assigned into treatment group and control group, with 50 patients in each group. In the treatment group 3 cases were lost to follow-up and one case was excluded, while in the control group 6 cases were lost to follow-up and 2 cases were excluded. Patients in the treatment group were treated with Liangxue Jiedu Huoxue Decoction in addition to radiotherapy， while patients in the control group were treated with radiotherapy alone. Main outcome measures: The incidence rates of radiation pneumonitis in the two groups were calculated. Acute radiation injury scoring criteria by Radiation Therapy Oncology Group (RTOG), clinical-radiographic-physiologic (CRP) score system, and Karnofsky Performance Status Scale (KPS) were used to evaluate the status of the patients. Results: The incidence rate of radiation pneumonitis was lower in the treatment group than in the control group (13.04% versus 33.33%, P＜0.05). According to the RTOG scale, the extent of lung injury was improved in the treatment group as compared with that in the control group (P＜0.05). The CRP score in the treatment group was significantly lower than that in the control group (P＜0.05). The KPS score in the treatment group was significantly higher than that in the control group (P＜0.05). Conclusion: Liangxue Jiedu Huoxue Decoction can decrease the incidence rate of radiation pneumonitis, reduce the extent of the lung injury, alleviate the symptoms of radiation pneumonitis, and improve life quality of the patients.
Source : Journal of Chinese Integrative Medicine: 2010; 8(7): 624-628 DOI: 10.3736/jcim20100704 LINK TO FULL ARTICLE
Oral Administration of Ren-Shen-Yang-Rong-Tang ‘Ninjin’yoeito’ Protects Against Hematotoxicity and Induces Immature Erythroid Progenitor Cells in 5-Fluorouracil-induced Anemia
Fumihide Takano,1 Yasuyuki Ohta,1 Tomoaki Tanaka,1 Kenroh Sasaki,2 Kyoko Kobayashi,2 Tomoya Takahashi,1 Nobuo Yahagi,1 Fumihiko Yoshizaki,2 Shinji Fushiya,3 and Tomihisa Ohta11Department of Pharmacognosy and Chemistry of Natural Products, Graduate School of Natural Science and Technology, Kanazawa University, Kanazawa, 22nd Department of Pharmacognosy, Tohoku Pharmaceutical University, Sendai and 3Department of Kampo Pharmaceutical Sciences, Nihon Pharmaceutical University, Saitama, Japan
The purpose of this study was to investigate the efficacy of four different Japanese and Chinese herbal prescriptions, Ren-Shen-Yang-Rong-Tang (Ninjin’yoeito, NYT), Chai-Hu-Gui-Zhi-Gan-Jiang-Tang (Saikokeishikankyoto, SKKT), Si-Jun-Zi-Tang (Shikunshito, SKT) and Si-Wu-Tang (Shimotsuto, SMT), which are traditionally used for anemia and fatigue, against hematotoxicity in mice treated with 5-fluorouracil (5-FU). NYT 1–100 mg kg–1 day–1 injected orally for 7 consecutive days before and after 5-FU injection significantly suppressed reductions in red blood cell, white blood cell and platelet counts in peripheral blood, and accelerated their recovery. Administration of SKKT also produced a slight but significant improvement in 5-FU-induced erythrocytopenia, whereas SMT and SKT could not prevent anemia. Oral injection of NYT also inhibited 5-FU-induced decreases in peripheral reticulocyte and bone marrow cell counts on day 10, and markedly hastened their recovery on day 20, in a dose-dependent manner. Erythroid progenitor colonies, such as colony forming units-erythroid and burst forming units-erythroid, formed by marrow cells from mice treated with 5-FU were significantly increased by oral administration of NYT. These findings suggest that NYT has the potential to protect against hematotoxicity, and also has hematopoietic activity, through stimulation of immature erythroid progenitor cell differentiation.
Abstract Background Skin toxicity is a common side effect of radiotherapy for solid tumors. Its management can cause treatment gaps and thus can impair cancer treatment. At present, in many countries no standard recommendation for treatment of skin during radiotherapy exists. In this study, we explored the effect of topically-applied tea extracts on the duration of radiation-induced skin toxicity. We investigated the underlying molecular mechanisms and compared effects of tea extracts with the effects of epigallocatechin-gallate, the proposed most-active moiety of green tea.
Methods Data from 60 patients with cancer of the head and neck or pelvic region topically treated with green or black tea extracts were analyzed retrospectively. Tea extracts were compared for their ability to modulate IL-1β, IL-6, IL-8, TNFα and PGE2 release from human monocytes. Effects of tea extracts on 26S proteasome function were assessed. NF-κB activity was monitored by EMSAs. Viability and radiation response of macrophages after exposure to tea extracts was measured by MTT assays.
Results Tea extracts supported the restitution of skin integrity. Tea extracts inhibited proteasome function and suppressed cytokine release. NF-κB activity was altered by tea extracts in a complex, caspase-dependent manner, which differed from the effects of epigallocatechin-gallate. Additionally, both tea extracts, as well as epigallocatechin-gallate, slightly protected macrophages from ionizing radiation
Conclusion Tea extracts are an efficient, broadly available treatment option for patients suffering from acute radiation-induced skin toxicity. The molecular mechanisms underlying the beneficial effects are complex, and most likely not exclusively dependent on effects of tea polyphenols such as epigallocatechin-gallate.
We conclude that tea extracts are efficient means to treat radiation-induced skin toxicity. Understanding the underlying molecular mechanisms in the future may establish tea extracts as a cheap and broadly available treatment for skin toxicity caused by ionizing radiation in industrial as well as developing countries during clinical radiotherapy and in case of accidents involving ionizing radiation.
1Division of Radiation Oncology, St. Gerardo Hospital, Monza, Milan 2Division of Surgery, St. Gerardo Hospital, Monza, Milan, 3Aloe Foundation, Isernia 4.I.N.R.C.A Laboratory of Analysis, Lecco, Italy Abstract Background: The recent advances in the analysis of tumor immunobiology suggest the possibility of biologically manipulating the efficacy and toxicity of cancer chemotherapy by endogenous or exogenous immunomodulating substances. Aloe is one of the of the most important plants exhibiting anticancer activity and its antineoplastic property is due to at least three different mechanisms, based on antiproliferative, immunostimulatory and antioxidant effects. The anti-proliferative action is determined by anthracenic and antraquinonic molecules, while the immunostimulating activity is mainly due to acemannan. Patients and Methods: A study was planned to include 240 patients with metastatic solid tumor who were randomized to receive chemotherapy with or without Aloe. According to tumor histotype and clinical status, lung cancer patients were treated with cisplatin and etoposide or weekly vinorelbine, colorectal cancer patients received oxaliplatin plus 5-fluorouracil (5-FU), gastric cancer patients were treated with weekly 5-FU and pancreatic cancer patients received weekly gemcitabine. Aloe was given orally at 10 ml thrice/daily. Results: The percentage of both objective tumor regressions and disease control was significantly higher in patients concomitantly treated with Aloe than with chemotherapy alone, as well as the percent of 3-year survival patients. Conclusion: This study seems to suggest that Aloe may be successfully associated with chemotherapy to increase its efficacy in terms of both tumor regression rate and survival time.
Radiation Protective Potentiality of Adhatoda vasica
Poonam Sharma1, Rajesh S. Jadon1, Dara Singh2, Ganesh N1*.
1*Dept. of Research, Jawaharlal Nehru Cancer Hospital & Research Centre, Idgah Hills, Bhopal 2Sher-e-Kashmir Institute of Medical Science, Srinagar Jammu & Kashmir.
Abstract The present study forecasts the extensive damage caused by radiotherapy and chemotherapy treatment for cancer in the genetic setup of an individual. To counteract this damage, radioprotective potentiality of 50% Methanolic extract of Adhatoda vasica was evaluated through Cyto-Geno analysis. 50% Methanolic extract of Adhatoda vasica leaves was used as a drug whose radioprotective potentiality was to be investigated. Human peripheral lymphocytes were cultured using RPMI-1640 media, harvested and observed under microscope for chromosomal aberration assay. Total 200 metaphases were counted for each group. All the metaphases were found to be normal in Control group. The frequency of normal metaphases greatly increased after pretreatment with both low and high drug dose (50mg/Kg body weight and 100mg/Kg body weight) concentration. The average normal metaphase in Radiation Control was 118 out of 200 metaphases but after pretreatment with 50% Methanolic extract of Adhatoda vasica the number of normal metaphase increased to 179 at 50mg/Kg body weight and 184 at 100mg/Kg body weight. It was concluded that 50% Methanolic Extract of Adhatoda vasica with both low and high drug doses have shown its potentiality as a radio protector against the therapeutically induced mutations which can prove to be a contributor in cancer management in future. Such indigenous Indian, herbal, cost effective, poor man friendly drug will definitely be a potential adjuvant to cancer treatments like radiotherapy and chemotherapy since Amifostine a well known radioprotector given to the patients at the time of cancer therapy is expensive and has its own side effects.
Protective effect of Bixa orellana L. against radiation induced chromosomal aberration in Swiss Albino Mice
M.S. Karchuli1, Ganesh N2
1VNS Institute of Pharmacy, Bhopal, M.P. India 2*Dept. of Research, Jawaharlal Nehru Cancer Hospital & Research Centre, Idgah Hills, Bhopal
Radioprotective effect of hydroalcoholic extract of seeds of Bixa orellana have been studied by examining chromosome aberration in cells of bone marrow in irradiated mice. Healthy adult Swiss mice were injected intraperitoneally (ip) with 500 mg kg–1 body weight, 1000 mg kg–1 of or double distilled water (DDW). They were exposed to whole body irradiation of 2.0 Gy gamma radiation 30 min later. After 24 h, chromosomal aberrations were studied in the bone marrow of the femur by routine metaphase preparation after colchicine treatment. Radiation (4.0 Gy) increased the number of aberrant cells from less than 1% in controls to almost 20%. Pre-treatment with the extract compounds resulted in a significant reduction in the percentage of aberrant metaphases as well as in the different types of aberration scored. The extract was not toxic at 1500 mg kg–1 body weight. Being non toxic and easily available natural source Bixa orellana extract may be use for as radioprotective for human beings.
ROLE OF ROSEMARY LEAF EXTRACT AGAINST VARIOUS DOSES OF GAMMA RADIATION
Garima Sancheti and P. K. Goyal* Radiation & Cancer Biology Laboratory, Department of Zoology, University of Rajasthan, Jaipur – 302 004 (India) Abstract
The present investigation reports the radiomodulatory effect of Rosmarinus officinalis (rosemary) leaf extract against radiation-induced hematological alterations in Swiss albino mice at various post-autopsy intervals (i.e., between 24 hours to day 30). Treatment of animals with rosemary extract (1000 mg/ kg body wt) prior to irradiation was found to delay the onset of mortality and reduced the symptoms of radiation sickness such as ruffled hairs, lethargy, anorexia and diarrhea in comparison to radiation alone treated animals. Rosemary treated experimental groups exhibited a dose dependent rise (9 < 6 < 3 Gy) in the number of leucocytes (i.e., lymphocytes, monocytes, basophils, eosinophils and neutrophils) by the 30th day post autopsy interval in comparison to the control. Irradiation resulted in a significant increase in lipid peroxidation levels (p< 0.01, p< 0.001) and a reduction in glutathione levels (p<0.05, p<0.001) in blood as observed in radiation alone treated animals. Conversely, treatment of mice with rosemary extract exhibited a significant decrease (p< 0.01, p< 0.001) in lipid peroxidation level and an increase (p< 0.05, p<0.001) in glutathione content.
The mechanism of the radioprotective action of Rosmarinus officinalis leaf extract in this animal model may thus be its free radical scavenging activity and its ability to thus protect cellular molecules from oxidative damage. Furthermore, it inhibited lipid peroxidation and modulated GSH levels in blood of these Swiss albino mice. The activity of rosemary may also be attributed to stimulating or protecting hematopoiesis in bone marrow and a subsequent increase of hematological constituents in the peripheral blood. Since significant protection was obtained at a non-toxic low dose, RE may have an advantage over the known radioprotectors. Further investigations are in progress to study the exact mechanism of action and clinical applicability of R. officinalis in radioprotection.
Oral complications are a common side effect of cancer chemotherapy,as antineoplastic agents affect both the immune system and the oral mucosa. This study demonstrates preventive and therapeutic effects of dental treatment and regular use of Weleda Ratanhia-Mundwasser®(herbal mouthwash) and Weleda Pflanzen-Zahngel® (herbaltoothgel) on oral mucositis during chemotherapy. Thirty-two female patients with breast cancer starting on chemotherapy were evaluated in this study. Plaque index, gingival index,degree of mucositis and 10 single symptoms were monitored once weekly for four consecutive weeks. After four weeks, plaqueand gingival indexes were slightly decreased compared to base line values. The degree of mucositis was increased by one grade in15.6 % of the patients and over 70 % remained without symptoms.On the whole, single symptoms decreased from day 7 since beginning of chemotherapy to day 28. Mucositis symptoms were moderate in severity, and the results indicate a positive influence ofusing Weleda Ratanhia-Mundwasser and Weleda Pflanzen-Zahngel.Further studies might be promising.
Ficus racemosa Stem Bark Extract: A Potent Antioxidant and a Probable Natural Radioprotector
V. P. Veerapur1, K. R. Prabhakar1, Vipan kumar Parihar1, Machendar Reddy Kandadi1, S. Ramakrishana2, B. Mishra4, B. S. Satish Rao2, K. K. Srinivasan3, K. I. Priyadarsini4 and M. K. Unnikrishnan1
1Department of Pharmacology, Manipal College of Pharmaceutical Sciences, 2Radiobiology, Kasturba Medical College, 3Department of Pharmaceutical Chemistry, Manipal College of Pharmaceutical Sciences, Manipal-576 104, Karnataka, India and 4Radiation and Photochemistry Division, Bhabha Atomic Research Centre, Mumbai-400085, India
Ethanol extract (FRE) and water extract (FRW) of Ficus racemosa(family: Moraceae) were subjected to free radical scavengingboth by steady state and time resolved methods such as nanosecond pulse radiolysis and stopped-flow spectrophotometric analyses.FRE exhibited significantly higher steady state antioxidantactivity than FRW. FRE exhibited concentration dependent DPPH,ABTS•–, hydroxyl radical and superoxide radical scavenging and inhibition of lipid peroxidation with IC50 comparable with tested standard compounds. In vitro radioprotective potentialof FRE was studied using micronucleus assay in irradiated Chinese hamster lung fibroblast cells (V79). Pretreatment with different doses of FRE 1h prior to 2 Gy -radiation resulted in a significant(P < 0.001) decrease in the percentage of micronucleatedbinuclear V79 cells. Maximum radioprotection was observed at20 µg/ml of FRE. The radioprotection was found to be significant(P < 0.01) when cells were treated with optimum dose of FRE(20 µg/ml) 1 h prior to 0.5, 1, 2, 3 and 4 Gy -irradiation compared to the respective radiation controls. The cytokinesis-block proliferative index indicated that FRE does not alter radiation induced cell cycle delay. Based on all these results we conclude that the ethanol extract of F. racemosaacts as a potent antioxidant and a probable radioprotector.