As a powerful antioxidant, vitamin C protects cells from oxidative damage by inhibiting production of free radicals. However, high levels of vitamin C shows cytotoxicity especially on cancerous cells through generating excessive ROS and blocking the energy homeostasis. Although the double-sided character of vitamin C has been extensively studied in many cell types, there is little research on the consequence of vitamin C treatment in stem cells. Here, we identified that high-dose vitamin C shows cellular toxicity on proliferating NSPCs. We also demonstrated that undifferentiated NSPCs are more sensitive to vitamin C-driven DNA damage than differentiated cells, due to higher expression of Glut genes. Finally, we showed that high-dose vitamin C selectively induces DNA damage on cancer stem cells rather than differentiated tumor cells, raising a possibility that vitamin C may be used to target cancer stem cells.

Excerpt: "Fruits or berries of Hippophae rhamnoides (sea buckthorn), a rich source of vitamins A, C, and E, carotenes, flavonoids, and microelements such as sulfur, selenium, zinc, and copper, are edible and have been shown to protect from atopic dermatitis, hepatic injury, cardiac disease, ulcer, and atherosclerosis. However, its mechanism of action is not clear. We show that Hippophae inhibits benzo(a)pyrene-induced forestomach and DMBA-induced skin papillomagenesis in mouse. This decrease in carcinogenesis may be attributed to the concomitant induction of phase II enzymes such as glutathione S-transferase and DT-diaphorase and antioxidant enzymes such as superoxide dismutase, catalase, glutathione peroxidase, and glutathione reductase in the mouse liver. This was accompanied by a remarkable induction of the transcription factor interferon regulatory factor-1 in the Hippophae-treated liver. Our results strongly suggest that Hippophae fruit is able to decrease carcinogen-induced forestomach and skin tumorigenesis, which might involve up-regulation of phase II and antioxidant enzymes as well as DNA-binding activity of IRF-1, a known antioncogenic transcription factor causing growth suppression and apoptosis induction for its anticancer effect.."

BACKGROUND:There is increasing interest in the possible association between cancer incidence and vitamin D through its role as a regulator of cell growth and differentiation. Epidemiological studies in adults and one paediatric study suggest an inverse association between sunlight exposure and cancer incidence.

METHODS:We carried out an ecological study using childhood cancer registry data and two population-level surrogates of sunlight exposure, (1) latitude of the registry city or population centroid of the registry nation and (2) annual solar radiation. All models were adjusted for nation-level socioeconomic status using socioeconomic indicators.

RESULTS:Latitude and radiation were significantly associated with cancer incidence, and the direction of association was consistent between the surrogates. Findings were not consistent across tumour types.

CONCLUSION:Our ecological study offers some evidence to support an association between sunlight exposure and risk of childhood cancer.

ABSTRACT: BACKGROUND: Many cancer patients seek homeopathy as a complementary therapy. It has rarely been studied systematically, whether homeopathic care is of benefit for cancer patients. METHODS: We conducted a prospective observational study with cancer patients in two differently treated cohorts: one cohort with patients under complementary homeopathic treatment (HG; n=259), and one cohort with conventionally treated cancer patients (CG; n=380). For a direct comparison, matched pairs with patients of the same tumour entity and comparable prognosis were to be formed. Main outcome parameter: change of quality of life (FACT-G, FACIT-Sp) after 3 months. Secondary outcome parameters: change of quality of life (FACT-G, FACIT-Sp) after a year, as well as impairment by fatigue (MFI) and by anxiety and depression (HADS). RESULTS: HG: FACT-G, or FACIT-Sp, respectively improved statistically significantly in the first three months, from 75.6 (SD 14.6) to 81.1 (SD 16.9), or from 32.1 (SD 8.2) to 34.9 (SD 8.32), respectively. After 12 months, a further increase to 84.1 (SD 15.5) or 35.2 (SD 8.6) was found. Fatigue (MFI) decreased; anxiety and depression (HADS) did not change. CG: FACT-G remained constant in the first three months: 75.3 (SD 17.3) at t0, and 76.6 (SD 16.6) at t1. After 12 months, there was a slight increase to 78.9 (SD 18.1). FACIT-Sp scores improved significantly from t0 (31.0 - SD 8.9) to t1 (32.1 - SD 8.9) and declined again after a year (31.6 - SD 9.4). For fatigue, anxiety, and depression, no relevant changes were found. 120 patients of HG and 206 patients of CG met our criteria for matched-pairs selection. Due to large differences between the two patient populations, however, only 11 matched pairs could be formed. This is not sufficient for a comparative study. CONCLUSION: In our prospective study, we observed an improvement of quality of life as well as a tendency of fatigue symptoms to decrease in cancer patients under complementary homeopathic treatment. It would take considerably larger samples to find matched pairs suitable for comparison in order to establish a definite causal relation between these effects and homeopathic treatment.

Data on the chemical composition of triterpenic and steroid compounds, isolated from the chaga mushroom grown in natural environment or in a synthetic culture have been summarized. Special attention has been paid to the biological activity of chaga mushroom extracts and these particular compounds against various cancer cell lines in vitro and in vivo. This analysis has demonstrated some common features in inhibition of growth of various cell lines by chaga mushroom components. In this context, the most active are triterpene compounds containing OH group at C-22 and a side chain unsaturated bond.

Adherence to traditional Mediterranean diet (MD) has been reported to be inversely associated with total, as well as cardiovascular, mortality. We have examined the relation between degree of such adherence and incidence of cancer overall in a general population sample of 25 623 participants (10 582 men, 15 041 women) of the Greek segment of the European Prospective Investigation into Cancer and nutrition (EPIC). All subjects completed a validated, interviewer-administered, semi-quantitative food-frequency questionnaire at enrolment. Degree of adherence to the traditional MD was assessed through a 10-point scale (0 minimal; 9 maximal) that incorporated key dietary characteristics. During a median follow-up of 7.9 years and 188 042 total person-years, 851 medically confirmed incident cancer cases (421 men, 430 women) were recorded. Using proportional hazards regression with adjustment for potential confounders, we found that a higher degree of MD adherence was associated with lower overall cancer incidence. A two-point increase in the score corresponded to a 12% reduction in cancer incidence (adjusted hazard ratio, 0.88 (95% confidence interval 0.80, 0.95)). The association was exposure-dependent and stronger among women. This inverse association with MD adherence was considerably stronger than that predicted on the basis of the associations of the individual components of this diet and points to the value of analysing dietary patterns in cancer studies.

Music is known to have the power to induce strong emotions. The present study assessed, based on Electroencephalography (EEG) data, the emotional response of terminally ill cancer patients to a music therapy intervention in a randomized controlled trial. A sample of 40 participants from the palliative care unit in the Hospital del Mar in Barcelona was randomly assigned to two groups of 20. The first group [experimental group (EG)] participated in a session of music therapy (MT), and the second group [control group (CG)] was provided with company. Based on our previous work on EEG-based emotion detection, instantaneous emotional indicators in the form of a coordinate in the arousal-valence plane were extracted from the participants' EEG data. The emotional indicators were analyzed in order to quantify (1) the overall emotional effect of MT on the patients compared to controls, and (2) the relative effect of the different MT techniques applied during each session. During each MT session, five conditions were considered:(initial patient's state before MT starts),(passive listening),(active listening),(relaxation), and(final patient's state). EEG data analysis showed a significant increase in valence (= 0.0004) and arousal (= 0.003) betweenandin the EG. No significant changes were found in the CG. This results can be interpreted as a positive emotional effect of MT in advanced cancer patients. In addition, according to pre- and post-intervention questionnaire responses, participants in the EG also showed a significant decrease in tiredness, anxiety and breathing difficulties, as well as an increase in levels of well-being. No equivalent changes were observed in the CG.

The effects of ascorbic acid and curcumin on quercetin-induced DNA damage, lipid peroxidation protein degradation were investigated in a model system of isolated rat-liver nuclei under aerobic conditions and in the presence of equimolar concentrations of iron or copper. Neither ascorbic acid nor curcumin inhibited quercetin-induced nuclear DNA damage, lipid peroxidation, or protein degradation. In fact, both antioxidants stimulated the oxidative damage to nuclear macromolecules. Ascorbic acid significantly increased the quercetin-induced nuclear DNA damage in the presence of either iron or copper. The increases in quercetin-induced nuclear lipid peroxidation and protein degradation by ascorbic acid were statistically significant only in the presence of iron or copper, respectively. Similarly, stimulation of quercetin-induced DNA damage and lipid peroxidation by curcumin was statistically significant only in the presence of copper or iron, respectively. Curcumin had no significant effect on nuclear protein degradation. These results demonstrate the pro-oxidant properties of ascorbic acid and curcumin, compounds that also demonstrate antioxidant and anticarcinogenic properties. Ascorbic acid and curcumin may therefore each have a dual role in carcinogenesis.

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.

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.

This systematic review analyzes current data on effects of exercise interventions and physical activity behavior on objective and subjective cancer related cognitive impairments (CRCI). Out of the 19 studies which met all inclusion criteria, five RCTs investigated rodents, whereas the other 14 trials explored humans and these included six RCTs, one controlled trial, two prospective noncontrolled trials, one case series, one observational study, and three cross-sectional studies. The results from animal models revealed positive effects of exercise during and after chemotherapy or radiation on structural alterations of the central nervous system, physiological as well as neuropsychological outcomes. The overall study quality in patient studies was poor. The current data on intervention studies showed preliminary positive effects of Asian-influenced movement programs (e.g., Yoga) with benefits on self-perceived cognitive functions as well as a reduction of chronic inflammation for breast cancer patients in the aftercare. Exercise potentially contributes to the prevention and rehabilitation of CRCI. Additional RCTs with standardized neuropsychological assessments and controlling for potential confounders are needed to confirm and expand preliminary findings.

Epidemiological evidence suggests that exercise improves survival in cancer patients. However, much is still unknown regarding the mechanisms of this positive survival effect and there are indications that exercise may not be universally beneficial for cancer patients. The key to understanding in which situations exercise is beneficial may lie in understanding its influence on the tumour microenvironment (TME)-and conversely, the influence of the tumour on physical functioning. The TME consists of a vast multitude of different cell types, mechanical and chemical stressors and humoral factors. The interplay of these different components greatly influences tumour cell characteristics and, subsequently, tumour growth rate and aggression. Exercise exerts whole-body physiological effects and can directly and indirectly affect the TME. In this chapter, we first discuss the possible role of exercise capacity ('fitness') and exercise adaptability on tumour responsiveness to exercise. We summarise how exercise affects aspects of the TME such as tumour perfusion, vascularity, hypoxia (reduced oxygenation) and immunity. Additionally, we discuss the role of myokines and other circulating factors in eliciting these changes in the TME. Finally, we highlight unanswered questions and key areas for future research in exercise oncology and the TME.

Our previous studies demonstrated that the combination of treatment with ascorbic acid (AsA) and X‑ray irradiation results in increased apoptosis in HL60 cells. The present study was performed to investigate the effects of the combined use of AsA and X‑ray irradiation on epithelial cancer and sarcoma cells, and its potential use in future clinical treatment. X‑ray irradiation combined withAsA treatment resulted in increased suppression of cell growth of HT1080, SAS and A549 cells in vitro compared with X‑ray irradiation alone. The combined treatment also suppressed tumor growth in implanted HT‑1080 cells in vivo. Using annexin V/propidium iodide staining and the detection ofactivated caspase 3, it was found that X‑ray irradiation increased the apoptotic rate of HT1080 cells and resulted in G2/M arrest. However, apoptosis in the HT1080 cells treated with 5 mM AsA remained unchanged, and no changes were observed in the G2/M fraction. By contrast, AsA treatment caused increased suppression of proliferation compared with X‑ray irradiation. These results suggested that 5 mM AsA slowed the cell cycle and reduced tumor growth. Therefore, X‑ray irradiation combined with AsA treatment may be effective against epithelial cancer and sarcoma cells.

OBJECTIVE:To collect preliminary data on the effects of Saam acupuncture with regard to the immunity in cancer patients.

METHODS:Ten cancer patients were analyzed for improvements in immunity. Acupuncture was applied at the 5 acupuncture points, Jingqu (LU 8), Zutonggu (BL 66), Yanggu (SI 5), Yangchi (TE 4), and Zhongwan (CV 12) for 2 weeks with 4 sessions. We assessed the effect of Korean Saam acupuncture on the immune system in cancer patients by measuring particular blood cell subsets, including CD3+, CD4+, CD8+, CD19+, and CD56+ cells, as well as total white blood cell count, absolute neutrophil count, and fatigue score. The measurement was performed before and after acupuncture and at a 2-week follow-up.

RESULTS:There was a statistically significant increase in the number of CD3+ (P = 0.023) and CD8+ cells (P<0.001) and T-cell subsets, as well as a decrease in the fatigue severity scale (FSS) score (P = 0.001) after Saam acupuncture using the 5 acupoints.

CONCLUSION:Acupuncture may improve the immune system by increasing the counts of a few immune cells and relieve fatigue in cancer patients by decreasing FSS scores. Although this was a non-controlled study, it constitutes preliminary research investigating the potential effects of Saam acupuncture in increasing the counts of several immune cells in cancer patients.

OBJECTIVE:To collect preliminary data on the effects of Saam acupuncture with regard to the immunity in cancer patients.

METHODS:Ten cancer patients were analyzed for improvements in immunity. Acupuncture was applied at the 5 acupuncture points, Jingqu (LU 8), Zutonggu (BL 66), Yanggu (SI 5), Yangchi (TE 4), and Zhongwan (CV 12) for 2 weeks with 4 sessions. We assessed the effect of Korean Saam acupuncture on the immune system in cancer patients by measuring particular blood cell subsets, including CD3+, CD4+, CD8+, CD19+, and CD56+ cells, as well as total white blood cell count, absolute neutrophil count, and fatigue score. The measurement was performed before and after acupuncture and at a 2-week follow-up.

RESULTS:There was a statistically significant increase in the number of CD3+ (P = 0.023) and CD8+ cells (P<0.001) and T-cell subsets, as well as a decrease in the fatigue severity scale (FSS) score (P = 0.001) after Saam acupuncture using the 5 acupoints.

CONCLUSION:Acupuncture may improve the immune system by increasing the counts of a few immune cells and relieve fatigue in cancer patients by decreasing FSS scores. Although this was a non-controlled study, it constitutes preliminary research investigating the potential effects of Saam acupuncture in increasing the counts of several immune cells in cancer patients.

Preclinical studies suggest that fasting prior to chemotherapy may be an effective strategy to protect patients against the adverse effects of chemo-toxicity. Fasting may also sensitize cancer cells to chemotherapy. It is further suggested that fasting may similarly augment the efficacy of oncolytic viral therapy. The primary mechanism mediating these beneficial effects is thought to relate to the fact that fasting results in a decrease of circulating growth factors. In turn, such fasting cues would prompt normal cells to redirect energy toward cell maintenance and repair processes, rather than growth and proliferation. However, fasting is also known to upregulate autophagy, an evolutionarily conserved catabolic process that is upregulated in response to various cell stressors. Here, we review a number of mechanisms by which fasting-induced autophagy may have an impact on both chemo-tolerance and chemo-sensitization. First, fasting may exert a protective effect by mobilizing autophagic components prior to chemo-induction. In turn, the autophagic apparatus can be repurposed for removing cellular components damaged by chemotherapy. Autophagy also plays a key role in epitope expression as well as in modulating inflammation. Chemo-sensitization resulting from fasting may in fact be an effect of enhanced immune surveillance as a result of better autophagy-dependent epitope processing. Finally, autophagy is involved in host defense against viruses, and aspects of the autophagic process are also often targets for viral subversion. Consequently, altering autophagic flux by fasting may alter viral infectivity. These observations suggest that fasting-induced autophagy may have an impact on therapeutic efficacy in various oncological contexts.

Aging constitutes the central risk factor for major diseases including many forms of cancer, neurodegeneration, and cardiovascular diseases. The aging process is characterized by both global and tissue-specific changes in gene expression across taxonomically diverse species. While aging has historically been thought to entail cell-autonomous, even stochastic changes, recent evidence suggests that modulation of this process can be hierarchal, wherein manipulations of nutrient-sensing neurons (e.g., in the hypothalamus) produce peripheral effects that may modulate the aging process itself. The most robust intervention extending lifespan, plausibly impinging on the aging process, involves different modalities of dietary restriction (DR). Lifespan extension by DR is associated with broad protection against diseases (natural and engineered). Here we review potential epigenetic processes that may link lifespan to age-related diseases, particularly in the context of DR and (other) ketogenic diets, focusing on brain and hypothalamic mechanisms.

The present paper assesses the modifying potential of black pepper on the hepatic biotransformation system in mice. The modulatory effect was assessed on glutathione S-transferase (GST), cytochrome b5 (cyt. b5), cytochrome P-450 (cyt. P-450), acid-soluble sulfhydryl (-SH) content and malondialdehyde (MDA) level. Swiss albino mice of either sex (eight weeks old) were fed on a diet containing 0.5%, 1% and 2% black pepper (w/w) for 10 and 20 days. The findings revealed a significant and dose-dependent increase in GST and -SH content in the experimental groups except the one maintained on 0.5% black pepper diet for 10 days. Elevated levels of cyt. b5 and cyt. P-450 were also statistically significant and dose-dependent. The level of MDA was lowered in the group fed on 2% black pepper diet for 20 days. Being a potential inducer of detoxication system, the possible chemopreventive role of black pepper in chemical carcinogenesis is suggested.

Exercise may be described as a polypill to prevent and/or treat almost every chronic disease, with obvious benefits such as its low cost and practical lack of adverse effects. Implementing physical activity interventions in public health is therefore a goal at the medical, social, and economic levels. This chapter describes the importance of health promotion through physical activity and discusses the impacts of exercise on the most prevalent chronic diseases, namely metabolic syndrome-related disorders, cardiovascular diseases, cancer, and Alzheimer's disease. For each of these chronic conditions, we discuss the epidemiological evidence supporting a beneficial role of exercise, provide guidelines for exercise prescription, and describe the biological mechanisms whereby exercise exerts its modulatory effects.