Updated: Aug 29, 2022
Upstream Thinking in Veterinary Oncology
Upstream Integrative Oncology can be thought of as a lifestyle approach which aims to create the conditions which support health and healing while also working to minimize tumor burden. It is about working toward creating an "Anticancer Life".
In an Upstream Integrative approach to cancer treatment, the work isn't done once conventional treatments are completed. The real work is just beginning. This is where lifestyle changes are implemented. This is where we focus on supporting life...on thriving.
Upstream thinking, in medicine, is an approach to patient care focused on the "upstream" causes of disease, using the analogy of a river. Beyond treating a current condition or diagnosis and the symptoms associated with it, an Upstream approach specifically aims to identify and correct the underlying causes of disease development and implement preventive measures whenever possible.
In the case of cancer, for example, what situations existed prior to development of cancer which allowed the disease to grow into a tumor in the first place? We all have cancer cells in our body. Why do some of us develop life-threatening disease and others do not? Is there anything we can do to address the environment in which the cancer developed in order to make it a less hospitable ecosystem for cancer growth? These are important questions. And they are questions at the forefront of research on cancer prevention.
In this article you will find:
Perspectives on Upstream Integrative Veterinary Oncology
Western Biomedicine Oncology: Tools & Training of a Medical Oncologist - a brief summary of western medical oncology training
Integrative Oncology: Tools & Training of this Upstream Oncologist - what got me interested in Integrative Oncology and my chosen tools, training and perspective
Introduction to Epigenetics and the potential role of Herbal Medicine in cancer patient care
a list of 62 research articles related to the ideas presented here, with links to the articles for your information and resources including...
Seven research articles evaluating Yunnan Pai Yao - a chinese herbal formula used to control bleeding - in companion animals
Upstream Oncology: A Model of Cancer Treatment and Patient Care
A comprehensive approach to health and well-being focuses on supporting optimal functioning of the body's natural healing processes, optimizing health and preventing disease, as well as implementing treatments once disease has occurred.
In oncology, upstream thinking is characterized by the understanding that, beyond tumor-directed treatments, it is important to consider what steps could be taken to support the body's natural defenses against cancer and what tools we have to make the body a less friendly environment for cancer cells. And, going a step further, to consider what we can do to improve the quality of life that is lived after a diagnosis of cancer.
Integrative Oncology leverages the advances of Western Biomedicine in downsizing the cancer burden while simultaneously utilizing the tools we have available to us in other systems of medicine to make the body a less hospitable environment for cancer and support the body's natural healing processes.
While there are many approaches that can be employed toward the fulfillment of these goals based on training and preference, treatments from both our Western biomedicine paradigm and other systems of medicine which may complement or fill in gaps in our current Western "conventional medicine" therapies can be considered.
Possibilities for intervention options outside the Western "conventional" medical oncology paradigm, which is heavily weighted toward pharmaceutical interventions, are particularly relevant to explore if one considers the limited options existing in the pharmaceutical formulary at this time which support the body's natural defenses and homeostasis mechanisms outside of treatments such as hormone supplementation, synthetic vitamins, intravenous fluids, blood transfusions and certain cancer "vaccines".
Research is accumulating on how diet, vitamin levels, exercise, lifestyle, stress, herbal medicines and acupuncture impact development of and recovery from cancer in humans. Recent studies also show that the health of the gut microbiome may impact individual responses to conventional cancer therapies like chemotherapy and immunotherapy.
We already use information from human medicine to inform conventional medicine developments in veterinary medicine and new pharmaceuticals. This research on lifestyle and botanical medicine from the human literature also informs new science-based perspectives in upstream integrative veterinary care and inspires veterinary research into these aspects of health and healing.
Inspired by research findings in human medicine, there is, recently, some published research evaluating the potential correlation between vitamin D and selenium levels and certain canine cancers. And veterinary research is being published in the past few years on on Yunnan Pai Yao, an herbal medicine used to treat bleeding and infection, as well as some bench top studies on issolated herbs and canine tumor cell lines.
It is in combining the strengths of the Western biomedicine paradigm and traditional medicine paradigms, which have a long history of supportive lifestyle and natural medicine therapies, that we open the door to improving outcomes for our cancer patients.
Supporting a Balanced Perspective
Cancer treatment is a multifaceted challenge. At the heart of this challenge lies the human component. The emotional and psychological trauma that often accompanies a diagnosis of cancer greatly affects the development of an optimal treatment plan for an individual patient or family. Individual family circumstances, belief systems and goals for the life of a family pet must be central to a compassionate approach to patient care.
One Approach to Integrative Oncology
Incorporating Traditional Chinese Medicine Interventions
Gut microbiome health
Select vitamins and supplements
Leveraging whole fresh foods as medicine
Lifestyle factors, exercise and weight management
Emotional health and wellbeing of the pet and family
Limiting exposure to avoidable toxins and carcinogens
Appropriate and thoughtfully applied western biomedicine cancer treatments
Western Biomedicine Oncology: Tools & Training of a Medical Oncologist
In the Western biomedicine paradigm (AKA "conventional" medicine), we oncologists are trained to use tools such as surgery, radiation, and chemotherapy in an attempt to rid the body of cancer cells. In this approach, treatments are aimed at either physically removing the cancer cells from the body, or damaging them in a way that they die or "commit suicide". This can work very well for certain types of cancer. But for other types of cancer with a high rate of spread (this is called metastasis) and high mortality rates, these treatments, while often providing an effective option to slow how quickly the cancer progresses in the body, frequently fail to achieve a cure. This tells us that cancer cells survive these treatments. These cells then begin to grow into more tumors.
To try and better address this reality and improve on our cancer treatment success, Western biomedicine has developed or is currently investigating other types of therapies which attempt to bolster immune response against cancer cells, starve the blood supply to the tumor cells, or target specific pathways involved in the growth of specific tumor types.
Beyond Surgery, Chemotherapy and Radiation
1) Metronomic chemotherapy: this type of treatment aims to inhibit the process of new blood vessel formation, called angiogenesis, that tumors need in order to supply nutrients needed to grow. This treatment can also make it harder for the tumor to hide from the immune system by changing certain immune responses involved in protecting tumor cells from immune system attack.
2) Immunotherapy: this type of treatment administers cancer "vaccines", for example, which are designed to help the immune system recognize cancer cells and clear them from the body.
3) Targeted therapies: this type of treatment is aimed at blocking or inhibiting specific signaling molecules or pathways that are involved in the growth of specific types of cancer.
These treatments are becoming more widespread in human oncology, and we do have some options available for veterinary patients. Many, however, can be limited by high cost, are not widely available, are still in the clinical trial phase, or are not effective in dogs and cats due to differences in their bodies or tumor types.
Principles of Combination Cancer Therapy
The principles of combination therapy in cancer treatment are to combine
anti-cancer treatments that do not have overlapping toxicities in order to effect greater tumor control.
There is a book called The Upstream Doctors by Rishi Manchanda published in 2013. When I read this book, I was impressed by many of the perspectives he presented. It was inspiring to hear these words from a human physician who was expressing one of the main motivations that brought me into the field of oncology in the first place.
Dr. Manchanda also did an 18 minute Ted Talk. In it he says:
"We need a fundamentally different way of looking at healthcare. We simply need a health care system that moves beyond looking at the symptoms that bring patients into clinics. But instead, actually, is able to look at and improve health where it begins. And where health begins is not in the four walls of the doctor's office, but where we live and where we work, where we eat, sleep, learn and play, where we spend the majority of our lives.
"It's not that doctors don't know these are important issues. In a recent survey of over 1000 physicians in the U.S, 80% of them said they know that their patients' upstream problems are as important as their medical problems. And despite that awareness of the importance of upstream issues, only one in five doctors said they had any sense of confidence to address those issues, to improve health where it begins."
Integrative Oncology: Tools & Training of this Upstream Oncologist
Motivation and Rationale
In implementing an Upstream approach to Oncology treatment and patient care, we consider what we can do to assist the patient's natural defenses and body processes in maintaining a healthy internal environment and to correct the imbalances that are promoting cancer persistence, growth and spread. This aspect of patient care is evolving rapidly in human medicine. It is becoming easier to find research looking into some of these aspects of wellness and healing.
One main way we can think about the effects of these lifestyle interventions scientifically is by understanding what are called "epigenetic" factors of disease. These, basically, are situations within the body which impact which genes within our DNA are actively contributing to the current state of the body. The factors affecting the dynamics of gene expression are many.
Cancer, at its root, is a chronic disease which is characterized by dysregulation of multiple body processes including chronic unmitigated inflammation, failure of appropriate immune responses, and aberrant molecular signaling which results in alteration of the body’s “ecosystem”. These changes in the internal environment of the body lead to epigenetic changes which ultimately result in altered gene expression, abnormal tissue growth and creation of a tumor microenvironment which supports the survival, growth and metastasis of these dysregulated cells. In many of our veterinary patients, cancer does not manifest appreciable signs until it is in its advanced stages or has become a life-threatening medical emergency.
Given that cancer is a multifactorial manifestation of disease, an effective approach to healing is multifactorial as well. Looking at the botanical medicine formulary, many herbs have been shown to mitigate inflammation in the body, inhibit angiogenesis and bolster anti-cancer immune responses. These parallel, and may support, the mechanisms of metronomic chemotherapy, immunotherapy and targeted cancer treatments. This should not be surprising given the fact that we currently use chemotherapy agents which are derived from plants, such as vincristine from the periwinkle plant and taxol from the Yew tree.
Additionally, herbs have application in alleviating side effects of conventional cancer therapies or clinical signs resulting from the cancer itself. These facts make them interesting options for care of the cancer patient.
Method and Perspective
In order to better understand and more effectively and safely utilize herbal therapies in my patient care, I chose to pursue additional training in Traditional Chinese Herbal Medicine (TCHM) and began the deep dive into the scientific literature on herbal medicine and cancer that is not a part of conventional Western biomedicine oncology training.
This interest in herbal medicine was initially sparked during my oncology residency when I simultaneously pursued training in veterinary acupuncture. It was during acupuncture training in 2005 that I learned about a few Chinese herbal formulas.
I had already been using Yunann Pai Yao to effectively palliate patients with bleeding tumors. I started implementing the new herbal formulas in practice for a few select end of life situations with surprising (to me anyway) results. The curiosity that was sparked by those experiences led me to pursue specific training in TCHM and, ultimately, a Graduate Diploma in Veterinary Chinese Herbal Medicine.
I find that Life, often, is my greatest teacher if I allow myself to be open to new ways of thinking and approaching problems, ask intelligent questions, think outside the box of my training or conditioning and do the work to find a sound balance between what I (or "we" as a veterinary profession) now know and what may be possible outside that current sphere of understanding. At that edge is growth. And that growth is a process, a journey of developing depth of understanding through inspired scientific inquiry and intelligent objective skepticism and discernment.
Yunnan Pai Yao
Yunnan Pai Yao is a Chinese herbal formula currently used by many veterinary oncologists who otherwise do not use Chinese herbal medicine because it is often effective in situations where we have limited conventional options. It is helpful in controlling bleeding and is commonly employed as a palliative treatment for patients with bleeding tumors, such as nasal tumors and hemangiosarcoma. Although research on it's hemostatic effects in animals can be found as far back as 1977, it is only in the last 2-3 years that veterinary studies have been published on its use in companion animals.
Chinese Herbal Therapies Modulate Epigenetic Changes
Epigenetic changes are known to influence the expression of genes which regulate tumor development. Specifically, deranged DNA and modification of histones have been shown to silence tumor suppressor genes and promote oncogenes. Three of these major epigenetic modifications are: DNA methylation, changes to chromatin, and noncoding RNA profiles. I'll write more on this later. For now, here are a few brief examples introducing the science behind the potential epigenetic role of Chinese Herbal Medicine in cancer patient care.
To use some familiar examples:
Studies have shown turmeric is able to restore expression of tumor suppressor genes.
Curcumin regulates histone acetylation in a beneficial way by inhibiting something called histone deacetylase (HDAC).
Berberine is one of the workhorse compounds found in many Chinese herbs prescribed for treatments of inflammation and management of cancer. It can be found in herbs such as Scutellaria (Chinese Skullcap), Bupleurum, Rhubarb, Coptis and Phellodendron. Berberine has been shown to reduce expression of transforming growth factor‐β (TGF‐β) and has been shown to inhibit cell migration and in vivo tumor growth in a number of studies. The TGF‐β signaling pathway regulates proliferation, invasion, and migration of cancer cells.
Berberine is under heavy investigation for its anticancer potential and there are hundreds of articles reporting additional effects on various tumor progression pathways. It has also demonstrated desirable effects on the tumor microenvironment including modulation of inflammatory processes and impacting the infiltration of immune cells into the tumor microenvironment. A quick pubmed search for "berberine cancer" will return over 850 research articles.
There is no question, if one takes the time to review the recent scientific literature on these topics, that the foods we eat, the herbs and pharmaceutical medicines we ingest, the emotions we repeatedly experience, and the chemicals we are chronically exposed to play a role in wellness and illness. It should come as no surprise, then, that the interventions most effective for any individual are dependent on the causes and conditions present in that patient's life and body.
It is my clinical experience that when lifestyle and nutritional interventions including diet, exercise, emotional wellness, select supplements, acupuncture and herbal medicines are appropriately implemented alongside thoughtfully applied patient-specific biomedicine therapies, patient well-being improves and often so do patient outcomes. When patient well-being improves, the experience of the whole patient care team becomes a more rewarding one.
The experience of cancer treatment can become one of empowerment and hope rather than despair and hopelessness.
Even in cases where "cure" isn't achieved, I have seen quality of life improve. I have seen patients live comfortably with their cancer for extended periods of time far beyond the prognosis we typically see with conventional treatments. I have seen prolonged disease stabilization with herbal treatments. And, although it doesn't happen for every patient, I have seen tumors shrink with aggressive herbal medicine and lifestyle interventions alone when our initial intent was palliative care.
Because our human healthcare system is not yet, in general, set up to support this type of wellness intervention, pet parents often don't know this is available in veterinary medicine. Due to lack of exposure, experience or training, it is also common for people to lack an understanding of the value in this way of approaching patient care, as well as the potential benefits and limitations.
A majority of my current clinical practice is Integrative Oncology. I enjoy being able to discuss these options with my clients. My personal approach specifically utilizes treatment modalities in which I have advanced training and experience, and so some degree of expertise: Western Biomedicine Oncology, Acupuncture and Chinese Herbal Medicine.
Upstream Interventions for Patient Care
1. Diet Incorporating Real Fresh Food as Medicine
Optimizing phytonutrients by including fresh vegetables, minimizing toxins and carcinogens being ingested; minimizing foods that may contribute to inflammation in the body; supporting the healthy bacteria in the gut (micro biome)
2. Regular Exercise
Exercise is helpful for immune system function and maintaining optimal body condition, as well as healthy metabolism
Research in humans has shown that stress hormones can contribute to cancer growth, an important topic when we consider how our stress levels may affect our pet's stress levels;
minimizing environmental and clinic-related stress
*Because I feel this is so important, I have recorded a webinar series on stress management practices for pet parents and veterinarians - registration is free
Herbal Medicine & Other
"Alternative Medicine" Interventions
1. Classical Chinese Herbal Medicine
Many herbs are adaptogens, immune modulators, and anti-inflammatory agents - there is much research emerging on anticancer effects of herbal compounds and some Chinese Herbal Formulas
Many herbs, for example, have shown the ability to block tumor progression pathways and angiogenesis (the process of new blood vessel formation)
An important option in palliative care, supporting appetite and energy, and minimizing side effects from conventional treatments or the cancer itself
3. Vitamins and other supplements
Supporting an Empowering Approach to Healing
As we develop a broader view of health and healing, we are empowered to take an active role in treatment, recovery and thriving.
Treatment then becomes not about a "battle against cancer" but about how we optimize life.
This focus is emotionally healthier for both veterinarians and pet guardians. Ultimately, it is a more effective approach to healing and support of the human-animal bond. It allows us to focus on wellness rather than focusing on disease. And, in the end, whether the cancer itself is the cause of death or whether it is eliminated, the quality of the life that is lived during the journey of cancer treatment is almost always improved.
For pet parents able to travel to Michigan, set up an Integrative Oncology Consultation (IOC) with me at OVRS.
For pets who can't travel to Michigan, I am now offering Integrative Oncology Telemedicine Consultations, working through a veterinarian local to you.
Chikara S, Nagaprashantha LD, Singhal J, et al. Oxidative stress and dietary phytochemicals: Role in cancer chemoprevention and treatment. Cancer Lett. 2018 Jan 28;413:122-134.
Sehrawat A, Roy R, Pore SK, et al. Mitochondrial dysfunction in cancer chemoprevention by phytochemicals from dietary and medicinal plants. Semin Cancer Biol. 2017 Dec;47:147-153.
Cragg GM, Pezzuto JM. Natural Products as a Vital Source for the Discovery of Cancer Chemotherapeutic and Chemopreventive Agents. Med Princ Pract. 2016;25 Suppl 2:41-59.
van Zelst M, Hesta M, Gray K, et al. Biomarkers of selenium status in dogs. BMC Vet Res. 2016 Jan 19;12:15.
Pilarczyk B, Tomza-Marciniak A, Pilarczyk R, et al. Relationship between serum Se concentration in dogs and incidence of some disease conditions. Cent Eur J Biol. 2013;8(6):527–33.
Waters DJ, Shen S, Glickman LT, Cooley DM, Bostwick DG, Qian J, et al. Prostate cancer risk and DNA damage: translational significance of selenium supplementation in a canine model. Carcinogenesis. 2005;26(7):1256–62.
Fico ME, Poirier KA, Watrach AM, Watrach MA, Milner JA. Differential effects of selenium on normal and neoplastic canine mammary cells. Cancer Res. 1986;46(7):3384–8.
Wallig MA, Kuchan MJ, Milner JA. Differential effects of cyanohydroxybutene and selenium on normal and neoplastic canine mammary cells in vitro. Toxicol Lett. 1993 Jul;69(1):97-105.
Weidner N, Woods JP, Conlon P, et al. Influence of Various Factors on Circulating 25(OH) Vitamin D Concentrations in Dogs with Cancer and Healthy Dogs. J Vet Intern Med. 2017 Nov;31(6):1796-1803.
Selting KA, Sharp CR, Ringold R, et al. Serum 25-hydroxyvitamin D concentrations in dogs - correlation with health and cancer risk. Vet Comp Oncol. 2016 Sep;14(3):295-305.
Sharp CR, Selting KA, Ringold R. The effect of diet on serum 25-hydroxyvitamin D concentrations in dogs. BMC Res Notes. 2015 Sep 15;8:442.
Yunnan Pai Yao - companion animal research
Ciepluch BJ, Wilson-Robles HM, Pashmakova MB, et al. Long-term postoperative effects of administration of allogeneic blood products in 104 dogs with hemangiosarcoma. Vet Surg. 2018 Nov;47(8):1039-1045.
Case Rep Vet Med. 2018 Feb 5;2018:6160980.
Tansey C, Wiebe ML, Hybki GC, et al. A prospective evaluation of oral Yunnan Baiyao therapy on thromboleastographic parameters in apparently healthy dogs. J Vet Emerg Crit Care (San Antonio). 2018 May;28(3):221-225.
Ness SL, Frye AH, Divers TJ, et al.Randomized placebo-controlled study of the effects of Yunnan Baiyao on hemostasis in horses. Am J Vet Res. 2017 Aug;78(8):969-976.
Lee A, Boysen SR, Sanderson J, et al. Effects of Yunnan Baiyao on blood coagulation parameters in beagles measured using kaolin activated thromboelastography and more traditional methods.
Int J Vet Sci Med. 2017 Apr 12;5(1):53-56.
Shmalberg J, Hill RC, Scott KC. Nutrient and metal analyses of Chinese herbal products marketed for veterinary use. J Anim Physiol Anim Nutr (Berl). 2013 Apr;97(2):305-14.
Ogle CW, Dai S, Cho CH. The hemostatic effects of orally administered Yunnan Bai Yao in rats and rabbits. Comp Med East West. 1977 Summer;5(2):155-60.
Scutellaria (Chinese Skullcap) and canine Osteosarcoma
Helmerick EC, Loftus JP, Wakshlag JJ. The effects of baicalein on canine osteosarcoma cell proliferation and death. Vet Comp Oncol. 2014 Dec;12(4):299-309.
Chinese Herbal Medicine:
So TH, Chan SK, Lee VH, et al. Chinese Medicine in Cancer Treatment - How is it Practised in the East and the West? Clin Oncol (R Coll Radiol). 2019 Jun 6.
Wang WJ, Zhang T. Integration of traditional Chinese medicine and Western medicine in the era of precision medicine. J Integr Med. 2017 Jan;15(1):1-7.
Bodeker G. Integrative oncology meets immunotherapy: new prospects for combination therapy grounded in Eastern medical knowledge. Chin J Integr Med. 2012 Sep;18(9):652-62.
Li X1, Yang G, Li X, et al. Traditional Chinese medicine in cancer care: a review of controlled clinical studies published in chinese. PLoS One. 2013;8(4):e60338.
Dobos GJ, Kirschbaum B, Choi KE. The Western model of integrative oncology: the contribution of Chinese medicine. Chin J Integr Med. 2012 Sep;18(9):643-51.
Ling CQ, Fan J, Lin HS, et al. Clinical practice guidelines for the treatment of primary liver cancer with integrative traditional Chinese and Western medicine. J Integr Med. 2018 Jul;16(4):236-248.
Epigenetic Changes in Cancer and the Potential Role of Chinese Herbs:
Xiang Y, Guo Z, Zhu P, et al. Traditional Chinese medicine as a cancer treatment: Modern perspectives of ancient but advanced science. Cancer Med. 2019 May;8(5):1958-1975.
Xu J, Long Y, Ni L, et al. Anticancer effect of berberine based on experimental animal models of various cancers: a systematic review and meta-analysis. BMC Cancer. 2019 Jun 17;19(1):589.
Sharma S, Kelly TK, Jones PA. Epigenetics in cancer. Carcinogenesis. 2010;31:27‐36.
Kanwal R, Gupta K, Gupta S. Cancer epigenetics: an introduction. Methods Mol Biol. 2015;1238:3‐25.
Fimognari C. Introduction to the Toxins Special Issue on Dietary and Non-Dietary Phytochemicals and Cancer. Toxins (Basel). 2016 Dec 28;9(1).
Wogan GN, Hecht SS, Felton JS, et al. Environmental and chemical carcinogenesis. Semin Cancer Biol. 2004 Dec;14(6):473-86.
Stress and Cancer:
Shin KJ, Lee YJ, Yang YR, et al. Molecular Mechanisms Underlying Psychological Stress and Cancer. Curr Pharm Des. 2016;22(16):2389-402.
Kennedy B, Fang F, Valdimarsdóttir U, et al. Stress resilience and cancer risk: a nationwide cohort study. J Epidemiol Community Health. 2017 Oct;71(10):947-953.
Kim-Fuchs C, Le CP, Pimentel MA, et al. Chronic stress accelerates pancreatic cancer growth and invasion: a critical role for beta-adrenergic signaling in the pancreatic microenvironment. Brain Behav Immun. 2014 Aug;40:40-7.
Lamkin DM, Sloan EK, Patel AJ, et al. Chronic stress enhances progression of acute lymphoblastic leukemia via β-adrenergic signaling. Brain Behav Immun. 2012 May;26(4):635-41.
Exercise and Cancer:
Idorn M, Thor Straten P. Exercise and cancer: from "healthy" to "therapeutic"? Cancer Immunol Immunother. 2017 May;66(5):667-671.
Pedersen L, Idorn M, Olofsson GH, et al. Voluntary Running Suppresses Tumor Growth through Epinephrine- and IL-6-Dependent NK Cell Mobilization and Redistribution. Cell Metab. 2016 Mar 8;23(3):554-62.
Schwartz AL, de Heer HD, Bea JW. Initiating Exercise Interventions to Promote Wellness in Cancer Patients and Survivors. Oncology (Williston Park). 2017 Oct 15;31(10):711-7.
Brown JC, Damjanov N, Courneya KS, et al. A randomized dose-response trial of aerobic exercise and health-related quality of life in colon cancer survivors. Psychooncology. 2018 Apr;27(4):1221-1228.
Mishra SI, Scherer RW, Snyder C, et al. Exercise interventions on health-related quality of life for people with cancer during active treatment. Cochrane Database Syst Rev. 2012 Aug 15;(8):CD008465.
Diet and Cancer:
Stepien M, Chajes V, Romieu I. The role of diet in cancer: the epidemiologic link. Salud Publica Mex. 2016 Apr;58(2):261-73.
Barak Y, Fridman D. Impact of Mediterranean Diet on Cancer: Focused Literature Review. Cancer Genomics Proteomics. 2017 Nov-Dec;14(6):403-408.
Grosso G, Buscemi S, Galvano F, et al. Mediterranean diet and cancer: epidemiological evidence and mechanism of selected aspects. BMC Surg. 2013;13 Suppl 2:S14.
Vergati M, Krasniqi E, Monte GD, et al. Ketogenic Diet and Other Dietary Intervention Strategies in the Treatment of Cancer. Curr Med Chem. 2017;24(12):1170-1185.
Pan JH, Abernathy B, Kim YJ, et al. Cruciferous vegetables and colorectal cancer prevention through microRNA regulation: A review. Crit Rev Food Sci Nutr. 2018;58(12):2026-2038.
Fujioka N, Fritz V, Upadhyaya P, et al. Research on cruciferous vegetables, indole-3-carbinol, and cancer prevention: A tribute to Lee W. Wattenberg. Mol Nutr Food Res. 2016 Jun;60(6):1228-38.
Popolo A, Pinto A, Daglia M, et al. Two likely targets for the anti-cancer effect of indole derivatives from cruciferous vegetables: PI3K/Akt/mTOR signalling pathway and the aryl hydrocarbon receptor. Semin Cancer Biol. 2017 Oct;46:132-137.
Morrison MEW, Joseph JM, McCann SE, et al. Cruciferous Vegetable Consumption and Stomach Cancer: A Case-Control Study. Nutr Cancer. 2019 May 16:1-10.
Mitsiogianni M, Koutsidis G, Mavroudis N, et al. The Role of Isothiocyanates as Cancer Chemo-Preventive, Chemo-Therapeutic and Anti-Melanoma Agents. Antioxidants (Basel). 2019 Apr 18;8(4).
Alsherbiny MA, Abd-Elsalam WH, El Badawy SA, et al. Ameliorative and protective effects of ginger and its main constituents against natural, chemical and radiation-induced toxicities: A comprehensive review. Food Chem Toxicol. 2019 Jan;123:72-97.
Stone TW, Darlington LG. Microbial carcinogenic toxins and dietary anti-cancer protectants. Cell Mol Life Sci. 2017 Jul;74(14):2627-2643.
Stone TW, McPherson M, Gail Darlington L. Obesity and Cancer: Existing and New Hypotheses for a Causal Connection. EBioMedicine. 2018 Apr;30:14-28.
Lee GA, Hwang KA, Choi KC. Roles of Dietary Phytoestrogens on the Regulation of Epithelial-Mesenchymal Transition in Diverse Cancer Metastasis. Toxins (Basel). 2016 May 24;8(6).
Panickar KS, Jewell DE. The beneficial role of anti-inflammatory dietary ingredients in attenuating markers of chronic low-grade inflammation in aging. Horm Mol Biol Clin Investig. 2015 Aug;23(2):59-70.
Pérez Alenza D, Rutteman GR, Peña L, et al. Relation between habitual diet and canine mammary tumors in a case-control study. J Vet Intern Med. 1998 May-Jun;12(3):132-9.
Martín-Ruiz A, Peña L, González-Gil A, et al. Effects of indole-3-carbinol on steroid hormone profile and tumor progression in a mice model of canine inflammatory mammary cancer. BMC Cancer. 2018 Jun 4;18(1):626.
Zhang Y, Lin L, Li H, et al. Effects of acupuncture on cancer-related fatigue: a meta-analysis. Support Care Cancer. 2018 Feb;26(2):415-425. doi: 10.1007/s00520-017-3955-6. Epub 2017 Nov 11.
Zia FZ, Olaku O, Bao T, et al. The National Cancer Institute's Conference on Acupuncture for Symptom Management in Oncology: State of the Science, Evidence, and Research Gaps. J Natl Cancer Inst Monogr. 2017 Nov 1;2017(52).
Chiu HY, Hsieh YJ, Tsai PS. Systematic review and meta-analysis of acupuncture to reduce cancer-related pain. Eur J Cancer Care (Engl). 2017 Mar;26(2).
Ben-Horin I, Kahan P, Ryvo L, et al. Acupuncture and Reflexology for Chemotherapy-Induced Peripheral Neuropathy in Breast Cancer. Integr Cancer Ther. 2017 Sep;16(3):258-262.
Bao T, Seidman AD, Piulson L, et al. A phase IIA trial of acupuncture to reduce chemotherapy-induced peripheral neuropathy severity during neoadjuvant or adjuvant weekly paclitaxel chemotherapy in breast cancer patients. Eur J Cancer. 2018 Sep;101:12-19.
Lau CH, Wu X, Chung VC, et al. Acupuncture and Related Therapies for Symptom Management in Palliative Cancer Care: Systematic Review and Meta-Analysis. Medicine (Baltimore). 2016 Mar;95(9):e2901.