Vinod Kochupillai

High Doses of Multiple Antioxidant Vitamins: Essential Ingredients in Improving the Efficacy of Standard Cancer Therapy

Numerous articles and several reviews have been published on the role of antioxidants, and diet and lifestyle modifications in cancer prevention. However, the potential role of these factors in the management of human cancer have been largely ignored. Extensive in vitro studies and limited in vivo studies have revealed that individual antioxidants such as vitamin A (retinoids), vitamin E (primarily alpha-tocopheryl succinate), vitamin C (primarily sodium ascorbate) and carotenoids (primarily polar carotenoids) induce cell differentiation and growth inhibition to various degrees in rodent and human cancer cells by complex mechanisms. The proposed mechanisms for these effects include inhibition of protein kinase C activity, prostaglandin E1-stimulated adenylate cyclase activity, expression of c-myc, H-ras, and a transcription factor (E2F), and induction of transforming growth factor-beta and p21 genes. Furthermore, antioxidant vitamins individually or in combination enhance the growth-inhibitory effects of x-irradiation, chemotherapeutic agents, hyperthermia, and biological response modifiers on tumor cells, primarily in vitro. These vitamins, individually, also reduce the toxicity of several standard tumor therapeutic agents on normal cells. Low fat and high fiber diets can further enhance the efficacy of standard cancer therapeutic agents; the proposed mechanisms for these effects include the production of increased levels of butyric acid and binding of potential mutagens in the gastrointestinal tract by high fiber and reduced levels of growth promoting agents such as prostaglandins, certain fatty acids and estrogen by low fat. We propose, therefore, a working hypothesis that multiple antioxidant vitamin supplements together with diet and lifestyle modifications may improve the efficacy of standard and experimental cancer therapies.

Antiemetic efficacy of ginger (Zingiber officinale) against cisplatin-induced emesis in dogs

Effect of ginger (Zingiber officinale Roscoe, Zingiberaceae) extracts (acetone, 50% ethanolic and aqueous) were investigated for antiemetic activity against emesis induced by 3 mg/kg cisplatin (the 100% emetic dose i.v.) in-healthy mongrel dogs. The acetone and 50% ethanolic extract at the doses of 25, 50, 100 and 200 mg/kg p.o. exhibited significant protection while aqueous extract at these doses was ineffective against cisplatin emesis. The acetone extract was more effective than ethanolic extract. However, both were less effective when compared to 5-HT3 receptors antagonist-granisetron. Neither of the ginger extract was effective against apomorphine-induced emesis. The findings suggest that ginger could be an effective and cheap antiemetic adjunct to cancer chemotherapy.

Sudarshan Kriya practitioners exhibit better antioxidant status and lower blood lactate levels

Oxidative stress may contribute to the pathophysiology of many chronic diseases. Since psychosocial stress increases oxidative stress, we conducted an exploratory study to investigate the effects of stress reduction with the Sudarshan Kriya (SK) program, on superoxide dismutase (SOD), catalase, glutathione and blood lactate levels in practitioners and non-practitioners of SK. Blood samples of ten practitioners of SK and 14 non-practitioners of any formal stress management technique were analyzed for SOD, catalase, glutathione and lactate levels. Differences between groups and subgroups were analyzed by t-test and correlations between variables compared using Pearsons correlation coefficient. Significantly lower levels of blood lactate (P=3.118e-10) and higher levels of SOD (P=0.0001415), glutathione (P=2.038e-06) and catalase (P=0.001565) were found in practitioners as compared to non-practitioners of SK, thereby suggesting that lower levels of blood lactate and better antioxidant status in practitioners are associated with regular practice of SK technique. However, this study needs to be conducted on a larger sample size to confirm this effect.

Chemotherapy alone vs. chemotherapy plus high dose multiple antioxidants in patients with advanced non small cell lung cancer.

Objective: In vitro and animal studies suggest that antitumor effect of chemotherapeutic agents may be enhanced by antioxidants. Therefore, we initiated a clinical study to test the efficacy of high-dose multiple antioxidants (vitamins C, E and beta carotene) as an adjunct to chemotherapy (paclitaxel and carboplatin) in non-small-cell lung cancer. Methods: 136 patients of stage IIIb and stage IV NSCLC were randomized to receive chemotherapy (paclitaxel and carboplatin) alone (chemotherapy arm, n = 72) or chemotherapy in combination with ascorbic acid 6100 mg/day, dl-alpha-tocopherol (vitamin E) 1050 mg/day and beta-carotene 60 mg/day (combination arm, n = 64). Survival were calculated by the Kaplan-Meier method and compared using the log-rank test. Results: An overall response rate (RR) of 33% was observed in chemotherapy arm with 24 patients showing a partial response (PR) and none showing a complete response (CR). In combination arm the overall RR was 37% with 24 patients showing PR and two showing CR. The median survival times in chemotherapy arm and combination arm were nine and 11 months respectively. The overall survival (OS) rates in chemotherapy arm and combination arm at one year were 32.9% and 39.1%, and at two years, 11.1% and 15.6% respectively. None of these differences were statistically significant (p = 0.20). Toxicity profiles were similar in both arms. Conclusions: These results do not support the concern that antioxidants might protect cancer cells from the free radical damage induced by chemotherapy. Larger trials are needed to demonstrate whether high-dose multiple antioxidants in conjunction with chemotherapy increase the response rates and/or survival time in advanced lung cancer.

Gene expression profiling in practitioners of Sudarshan Kriya

BACKGROUND The rapid pace of life, eating habits, and environmental pollution have increased stress levels and its related disorders. The complex molecular response to stress is mediated by stress genes and a variety of regulatory pathways. Oxidative stress is internal damage caused by reactive oxygen species. Increasing evidence suggests that chronic psychosocial stress may increase oxidative stress, which in turn may contribute to aging, and etiology of coronary diseases, cancer, arthritis, etc. Psychophysiological concomitants of meditation have been extensively researched, but there are very little data available on biochemical activity leading to relieving stress by causing a relaxation response by Sudarshan Kriya (SK). SK is a breathing technique that involves breathing in three different rhythms. It is preceded by Ujjayi Pranayam (long and deep breaths with constriction at the base of throat) and Bhastrika (fast and forceful breaths through nose along with arm movements). METHODS Forty-two SK practitioners and 42 normal healthy controls were recruited for our study. The practitioners had practiced SK for at least 1 year. Selected normal healthy controls did not perform any conventional physical exercise or any formal stress management technique. Whole blood was used for glutathione peroxidase estimation and red blood cell lysate was used for superoxide dismutase activity assay and for glutathione estimation. White blood cells were isolated from fresh blood and assayed for gene expression using reverse transcriptase-polymerase chain reaction. The parameters studied are antioxidant enzymes, genes involved in oxidative stress, DNA damage, cell cycle control, aging, and apoptosis. RESULTS A better antioxidant status both at the enzyme activity and RNA level was seen in SK practitioners. This was accompanied by better stress regulation and better immune status due to prolonged life span of lymphocytes by up-regulation of antiapoptotic genes and prosurvival genes in these subjects. CONCLUSIONS Our pilot study provides the first evidence suggesting that SK practice may exert effects on immunity, aging, cell death, and stress regulation through transcriptional regulation.

Effect of rhythmic breathing (Sudarshan Kriya and Pranayam) on immune functions and tobacco addiction.

Stress, a psychophysiological process, acts through the immune‐neuroendocrine axis and affects cellular processes of body and immune functions, leading to disease states including cancer. Stress is also linked to the habit of tobacco consumption and substance abuse, which in turn also leads to diseases. Sudarshan Kriya (SK) and Pranayam (P), rhythmic breathing processes, are known to reduce stress and improve immune functions. Cancer patients who had completed their standard therapy were studied. SK and P increased natural killer (NK) cells significantly (P <0.001) at 12 and 24 weeks of the practice compared to baseline. Increase in NK cells at 24 weeks was significant (P <0.05) compared to controls. There was no effect on T‐cell subsets after SK and P either in the study group or among controls. SK and P helped to control the tobacco habit in 21% of individuals who were followed up to 6 months of practice. We conclude that the inexpensive and easy to learn and practice breathing processes (SK and P) in this study demonstrated an increase in NK cells and a reduction in tobacco consumption. When confirmed in large and randomized studies, this result could mean that the regular practice of SK and P might reduce the incidence and progression of cancer.

Cutaneous metastases of lung cancer.

The reported incidence of skin metastases from lung cancer varies from 2.8-7.5%. In the present study 8.7% of patients had skin metastases, with head and neck being the most common sites, nodular lesions the most common, and adenocarcinoma the most frequent histology. Although most patients develop these lesions during the course of a known progressive disease, they may be the presenting manifestation of a primary tumour in the lung. The occurrence of skin lesions in lung cancer announces an ominous prognosis. The response to chemotherapy is poor, possibly due to poor blood supply to the skin; monitoring response to chemotherapy, however, is easier when such lesions are present.

Potentiation of the Effect of Paclitaxel and Carboplatin by Antioxidant Mixture on Human Lung Cancer H520 Cells

Objective: Antioxidants have been shown to enhance the effect of certain chemotherapeutic agents on tumor cells in culture. However, this effect differs depending upon the type of tumor and the drugs. In this study, the objective was to see whether pretreatment with antioxidant mixture could enhance the cytotoxic and apoptotic effect of commonly used chemotherapeutic agents, paclitaxel and carboplatin for the treatment of NSCLC. Methods: Human lung squamous cell carcinoma cell line, H520, was treated with antioxidant mixture (vitamin C, vitamin E and beta carotene), paclitaxel and carboplatin, individually and in combination of different doses in different sequences. Growth inhibition and induction of apoptosis was studied by morphological changes, MTT assay and flow-cytometric analysis. Results: The antioxidant mixture by itself led to 15% apoptosis in H520 cells. Paclitaxel treatment 24 hours prior to carboplatin caused 54% apoptosis, more than that produced by simultaneous treatment with both agents (40%). A statistically significant improvement in the degree of apoptosis, induced by paclitaxel and carboplatin combination, was seen when the cells were pretreated with antioxidant mixture immediately before paclitaxel exposure (70%) or 24 hours before paclitaxel exposure (89%). Conclusion: The data suggests that the apoptotic effects of paclitaxel and carboplatin are enhanced by pretreatment with the antioxidant mixture. Thus, the most promising sequence of these agents, which emerged in this study, was pretreatment with antioxidant mixture for 24 hours followed by paclitaxel treatment for 24 hours followed by carboplatin exposure for 24 hours.

Fetal liver transplantation

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Lympho-hemopoietic malignancies in India

Available information on lympho-hemopoietic malignancies in India is presented. The incidence of most cancers, including multiple myeloma, lymphomas, and leukemias, is lower compared to that in the West; chronic myelogenous leukemia, however, is higher and the incidence of non-Hodgkin’s lymphoma (NHL) is rising. Most cancers occur at a younger age. Higher frequencies of mixed-cellularity Hodgkin’s disease, diffuse large-cell NHL and T cell acute lymphoblastic leukemia are noted. Most patients present in advanced stages and have poorer prognostic factors. Treatment results are comparable if stagewise distribution and poor prognostic factors are taken into account.