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Bishayee A.,Larkin Health science Institute | Block K.,Block Center for Integrative Cancer Treatment
Seminars in Cancer Biology | Year: 2015

Despite exciting advances in targeted therapies, high drug costs, marginal therapeutic benefits and notable toxicities are concerning aspects of today's cancer treatments. This special issue of Seminars in Cancer Biology proposes a broad-spectrum, integrative therapeutic model to complement targeted therapies. Based on extensive reviews of the cancer hallmarks, this model selects multiple high-priority targets for each hallmark, to be approached with combinations of low-toxicity, low-cost therapeutics, including phytochemicals, adapted to the well-known complexity and heterogeneity of malignancy. A global consortium of researchers has been assembled to advance this concept, which is especially relevant in an era of rapidly expanding capacity for genomic tumor analyses, alongside alarming growth in cancer morbidity and mortality in low- and middle-income nations. © 2015 Elsevier Ltd. Source

Yang P.,University of Texas M. D. Anderson Cancer Center | Cartwright C.,University of Texas M. D. Anderson Cancer Center | Chan D.,University of Texas M. D. Anderson Cancer Center | Ding J.,University of Texas M. D. Anderson Cancer Center | And 7 more authors.
Molecular Carcinogenesis | Year: 2014

The beneficial effects of omega-3 fatty acids are believed to be due in part to selective alteration of arachidonate metabolism that involves cyclooxygenase (COX) enzymes. Here we investigated the effect of eicosapentaenoic acid (EPA) on the proliferation of human non-small cell lung cancer A549 (COX-2 over-expressing) and H1299 (COX-2 null) cells as well as their xenograft models. While EPA inhibited 50% of proliferation of A549 cells at 6.05μM, almost 80μM of EPA was needed to reach similar levels of inhibition of H1299 cells. The formation of prostaglandin (PG)E3 in A549 cells was almost threefold higher than that of H1299 cells when these cells were treated with EPA (25μM). Intriguingly, when COX-2 expression was reduced by siRNA or shRNA in A549 cells, the antiproliferative activity of EPA was reduced substantially compared to that of control siRNA or shRNA transfected A549 cells. In line with this, dietary menhaden oil significantly inhibited the growth of A549 tumors by reducing tumor weight by 58.8±7.4%. In contrast, a similar diet did not suppress the development of H1299 xenograft. Interestingly, the ratio of PGE3 to PGE2 in A549 was about 0.16 versus only 0.06 in H1299 xenograft tissues. Furthermore, PGE2 up-regulated expression of pAkt, whereas PGE3 downregulated expression of pAkt in A549 cells. Taken together, the results of our study suggest that the ability of EPA to generate PGE3 through the COX-2 enzyme might be critical for EPA-mediated tumor growth inhibition which is at least partly due to down-regulation of Akt phosphorylation by PGE3. © 2013 Wiley Periodicals, Inc. Source

Baak J.P.A.A.,University of Stavanger | Baak J.P.A.A.,Fudan University | Gyllenhaal C.,University of Texas M. D. Anderson Cancer Center | Liu L.,Fudan University | And 3 more authors.
Integrative Cancer Therapies | Year: 2011

Recent studies based on epidemiological models published in this journal and elsewhere have demonstrated encouraging patterns suggesting that herbal treatment may improve prognosis in advanced colon and lung cancer patients. Various problems exist with data from nonrandomized studies of this type, but a strong signal of potential positive effect can be seen. The therapeutic mechanisms of traditional Chinese medicine in metastatic cancer are discussed against a hypothetical, dualistic antiproliferation model and immune-stimulation model of tumor progression and regression. Recommendations are made for a strategy to demonstrate more conclusively the efficacy of adjunct herbal treatment during cancer chemotherapy and for discussions with patients until such time as the efficacy trials are completed. © SAGE Publications 2011. Source

Frenkel M.,University of Houston | Abrams D.I.,San Francisco General Hospital | Ladas E.J.,Columbia University | Deng G.,Sloan Kettering Cancer Center | And 7 more authors.
Integrative Cancer Therapies | Year: 2013

Many studies confirm that a majority of patients undergoing cancer therapy use self-selected forms of complementary therapies, mainly dietary supplements. Unfortunately, patients often do not report their use of supplements to their providers. The failure of physicians to communicate effectively with patients on this use may result in a loss of trust within the therapeutic relationship and in the selection by patients of harmful, useless, or ineffective and costly nonconventional therapies when effective integrative interventions may exist. Poor communication may also lead to diminishment of patient autonomy and self-efficacy and thereby interfere with the healing response. To be open to the patient's perspective, and sensitive to his or her need for autonomy and empowerment, physicians may need a shift in their own perspectives. Perhaps the optimal approach is to discuss both the facts and the uncertainty with the patient, in order to reach a mutually informed decision. Today's informed patients truly value physicians who appreciate them as equal participants in making their own health care choices. To reach a mutually informed decision about the use of these supplements, the Clinical Practice Committee of The Society of Integrative Oncology undertook the challenge of providing basic information to physicians who wish to discuss these issues with their patients. A list of leading supplements that have the best suggestions of benefit was constructed by leading researchers and clinicians who have experience in using these supplements. This list includes curcumin, glutamine, vitamin D, Maitake mushrooms, fish oil, green tea, milk thistle, Astragalus, melatonin, and probiotics. The list includes basic information on each supplement, such as evidence on effectiveness and clinical trials, adverse effects, and interactions with medications. The information was constructed to provide an up-to-date base of knowledge, so that physicians and other health care providers would be aware of the supplements and be able to discuss realistic expectations and potential benefits and risks. © 2013 The Author(s). Source

Jensen L.D.,Linkoping University | Jensen L.D.,Karolinska Institutet | Gyllenhaal C.,Block Center for Integrative Cancer Treatment | Block K.,Block Center for Integrative Cancer Treatment
Biomolecular Concepts | Year: 2014

Daily rhythms of light/darkness, activity/rest and feeding/fasting are important in human physiology and their disruption (for example by frequent changes between day and night shifts) increases the risk of disease. Many of the diseases found to be associated with such disrupted circadian lifestyles, including cancer, cardiovascular diseases, metabolic disorders and neurological diseases, depend on pathological de-regulation of angiogenesis, suggesting that disrupting the circadian clock will impair the physiological regulation of angiogenesis leading to development and progression of these diseases. Today there is little known regarding circadian regulation of pathological angiogenesis but there is some evidence that supports both direct and indirect regulation of angiogenic factors by the cellular circadian clock machinery, as well as by circulating circadian factors, important for coordinating circadian rhythms in the organism. Through highlighting recent advances both in pre-clinical and clinical research on various diseases including cancer, cardiovascular disorders and obesity, we will here present an overview of the available knowledge on the importance of circadian regulation of angiogenesis and discuss how the circadian clock may provide alternative targets for pro- or anti-angiogenic therapy in the future. © 2014 by Walter de Gruyter Berlin/Boston. Source

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