Abstract
Plant-based diets have long been one of the pillars of patient care in integrative cancer clinics. Their benefits have been endorsed even by the American Cancer Society, which, in its 2012 cancer prevention guidelines, encourages patients to “consume a healthy diet, with an emphasis on plant foods.” 1 In December 2014, we saw the passing of Michio Kushi, a true pioneer in advocating the role of plant-based diets in cancer prevention and treatment, and a major figure in the field of complementary and alternative cancer therapies. His highly influential macrobiotic lifestyle has received global attention. His 1983 book, The Cancer Prevention Diet, was widely noted as an early model for dietary and lifestyle interventions for cancer. Kushi first arrived in the United States in 1949, and by the 1960s had developed a strong interest in diet and health, formulating his macrobiotic program. Kushi and his wife Aveline founded the Kushi Institute in Brookline, Massachusetts, and there are now 3 more Kushi Institutes internationally. Residential and career-oriented programs at the institute provide counseling for patients and train macrobiotic practitioners. He also founded Erewhon, one of the first natural foods companies in the United States. His son Haruo (Larry) Kushi went on to become a well-known epidemiological researcher in the area of diet and health. 1 Despite an approach that was controversial for many in the medical community, Kushi leaves a legacy of focusing on diet as cancer therapy that has played a significant role in turning the attention of nutritional science to the ways that food and lifestyle choices truly support physical and emotional healing for cancer patients.
This issue begins with an editorial commentary on the effects of integrative therapies on molecular targets of interest in cancer. Molecular target therapies are taking a predominant role in cancer treatment, especially since the ability to sequence the cancer genome has revolutionized the way we search for drug targets. These therapies, however, typically affect only a small number of the genetic alterations in an individual tumor, and resistance to their effects frequently sets in after only months of use. Antiresistance therapies are needed that are based on targeting of multiple growth pathways in cancer. We feel that lifestyle therapies—diet, exercise, and biobehavioral—offer promise in this area, with the potential to modify many targets from a single intervention. Our commentary briefly reviews some relevant literature in this area, which is one that we hope will attract more research in the future.
Erin Sweet and colleagues from Bastyr University and Fred Hutchinson Cancer Research Center surveyed breast cancer patients about their use of herbs and supplements around the time of surgery to estimate the prevalence of patients’ use of substances that might promote excessive bleeding during surgery. This important topic deserves attention from clinicians who work with any type of cancer. One interesting fact that the authors note is that they did not include fish oil or flax oil among their supplements that might cause bleeding, since, in fact, these have been shown not to promote excess bleeding in spite of their anti-inflammatory qualities.
Exercise is being increasingly promoted for cancer patients as a way to improve quality of life as well as disease outcomes. Naciye Vardar Yagli of Hacettepe University in Ankara, Turkey, reports a randomized trial in breast cancer patients in which aerobic exercise is compared with aerobic exercise accompanied by yoga. Both groups experienced a number of benefits from exercise, but it was in the important area of fatigue perception that yoga appears to have made a distinguishably better contribution.
Ai Guang Zhao and Ni Da Cao and colleagues from Shanghai hospitals explored the use of traditional Chinese herbal medicine (TCHM) in combined Western–TCHM treatment of pancreatic cancer. They used an epidemiological model for this investigation, comparing outcomes of patients at these hospitals who received TCHM treatment with those who did not. The specific TCHM treatment used was a formula that contained, among other herbs, citrus peel, pinellia, and zedoary, a plant in the same genus as turmeric, which is well known for its anticancer properties.
Mistletoe therapy is widely used in complementary cancer treatment in Europe, and a large number of studies have been published on its use. A novel intratumoral method of administration has recently been explored, as published in this journal in 2013. 2 The same research group, led by Friedeman Schad of the Research Institute Havelhoehe in Berlin, is presenting in the present issue a comprehensive assessment of adverse reactions to the intratumoral protocol, which fortunately appear to be few in number.
The effect of dietary fat in carcinogenesis has long been a topic of interest. The amount of dietary fat has most frequently been debated, but the type of fat is also a question of importance. Maria Ramírez-Expósito and colleagues at the University of Jaén in Jaén, Spain, present an animal study of the effects of fat type at normal dietary fat levels. They specifically look at olive oil and oleic acid–enriched sunflower oil and their effects on the renin–angiotensin system. The renin–angiotensin system regulates blood pressure, but researchers are increasingly investigating its effects in cancer.
Cancer stem cells appear to be responsible not only for the genesis of tumors but also for part of their drug resistance. A special population of cancer stem cells, the “side population,” is particularly enriched in the ATP-binding cassette drug efflux pumps that remove chemotherapy drugs from resistant cancer cells. Annapoorni Rangarajan from the Indian Institute of Sciences and colleagues have examined the effects of 2 traditional Indian herbal remedies, Withania somnifera and Tinospora cordifolia, on this side population. The development of nontoxic herbal formulas that could be used alongside chemotherapy to inhibit the appearance of drug resistance is an attractive prospect, and the results of this study are quite encouraging.
Girija Kuttan and colleagues at the Amala Cancer Research Institute have examined the use of the Indian traditional herb Curculigo orchioides alongside cyclophosphamide in an animal tumor model. This herb is known for its anti-inflammatory and immune stimulatory properties. The investigators report not only an improvement in tumor suppression with the herbal therapy but also a reversal of drug-induced immune suppression, a reduction in serum inflammatory cytokines, and an antioxidant effect through lowering of lipid peroxides. The anti-inflammatory and antioxidant effects are especially interesting, suggesting that the presence of antioxidant effects does not necessarily inhibit chemotherapeutic activity.
In another demonstration of synergistic effects of herbal antioxidants and chemotherapy, Hsiu-O Hu and colleagues at Taipei Medical University tested the effects of resveratrol, curcumin, and a fungal extract co-administered with doxorubicin on normal fibroblasts and breast cancer cells. In addition to exerting protective effects on normal cells, the herbal extracts improved the cell-killing ability of doxorubicin in the breast cancer cells. Antioxidant effects were documented in the normal cells. This study and the study by Kuttan et al both show that the assumption that antioxidant substances will inevitably interfere with chemotherapy activities has to be questioned, especially in the use of complex botanical compounds that are known to target multiple activities relevant to cancer.
To conclude, we would like to acknowledge the many researchers who participated in our article review process during 2014. Reviewers like these are critical in maintaining the integrity of scientific publication, and we are profoundly grateful to them for their contribution to this journal. Our 2014 reviewers are the following: Ausaf Ahmad, Jean Alvarez, S. Arora, Kristen Arthur, Margaret Rinehart Ayres, Tao Bai, Barbara Baker, Fátima Baltazar, Yanju Bao, Devon Baxter, Rajaa El Bekay, Izabela Berdowski, Biswa Biswal, Felicity Bishop, Elfriede Bollschweiler, Dirk Buchwald, Susan Butler, Zhiyun Cao, Linda Carlson, Pei-Ni Chen, W. C. Cho, Paul Clark, Misha Cohen, Holger Cramer, Yue Dai, Zhi-Jun Dai, Mellar Davis, Joshua Denham, J. Dong, Patrick Dougherty, Gary Elkins, Mark Erian, Erin Fekete, Laurette Ferraresi, Brian Focht, Sarah Fogarty, Dunne Fong, Jennifer Sandson Frank, Sheila Garland, Rachel Gibson, Maria Goossens, Catherine Granger, Azizul Haque, Julieanne Hilbers, Caroline Hoffman, Yoshio Honma, Seyed J. Hosseinimehr, Ying Huang, Fazlul Huq, M. Igci, Linda Jacobs, Shamini Jain, Jong Soo Jeong, Xingzhong Jin, Georgios Kallifatidis, Nadja Klafke, Ari Koivisto, Miha Kovačič, Neeta Kumar, Hsing-Chung Kuo, Deep Kwatra, Gi-Ming Lai, David Larkin, Hong Jin Lee, J. Lee, Li Li, Shao Li, Yan Li, Chia-Chin Lin, Christopher Lis, Jianxun Liu, V. Lokanthana, Michael Mackenzie, Y. Maehara, Michelle Martinez-Montemayor, Matthew Maurer, R. Maunder, Michael McCulloch, Christine McDonald, Mark Mead, Steven Melnick, Hashim Mileik, S. Mishra, Ralph Moss, Ralph Muecke, Gnanasekar Munirathinan, Mohd Nasser, Sheryl Ness, Susan Olivo-Marston, Lise Paquet, Giulana Pelicci, Kara Perrow, Giovanna Petrangolini, E. Philip, P. Pratheeshkumar, Morten Quist, Heather Ray, Raghavendra Rao, Chris Repka, Philip Reuter, Jose Rodriquez, Waheed Roomi, Rebecca Roubin, M. De Ruiter, D. Sadava, Yasuyuki Sadzuka, Stephen Sagar, Anita Salamonsen, Deborah Santos, Julie Schnurr, Marilia Seelaender, Mehdi Shakibaei, Neetu Singh, Daniel Sliva, Judith Smith, Lisa Sprod, Brenda Stephenson, Frederick Stiefel, Robert Stoehr, Shaida Sulaiman, Erin Sweet, Karen Swenson, Y. Tang, Cynthia Thomson, Venkataswarup Tiriveedhi, Gabriela Trevisan, Jacob Uth, Carmina Valle, Sara Vargas, Flávia Vida, Massimiliano Visocchi, Jun Wang, Won-Bo Wang, Jon Wardle, Siobhan White, Jennifer Wiernikowski, Carla Wilson, Linda Witek-Janusek, Mostafa Yakoot, N. Yalindag, Kehu Yang, Hwa Seung Yoo, Seong Woo Yoon, Tatsuya Yoshida, Haiping Zhao, Wen-En Zhao, Xiangsheng Zuo.
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