BACKGROUND:Although several therapeutic options are currently available for patients with various cancers, the outcomes are often disappointing and a more effective modality needs to be promptly established. We have been exploring an alternative approach using natural agents and two bioactive mushroom extracts isolated from Phellinus linteus (PL), namely PL-ES and PL-I-ES, were of our interest. As anticancer effects of similar extracts have been reported in several cancers, we investigated whether PL-ES and PL-I-ES might have such anticancer activities on a variety of human cancer cells in vitro.

METHODS:Ten different types of human cancer cell lines, including three metastatic prostate, bladder, kidney, lung, breast, stomach, liver, and brain cancer cells, were employed and tested with PL-ES or PL-I-ES. Cell growth/viability, exertion of oxidative stress, and induction of apoptosis were assessed by MTT (3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl-tetrazolium bromide) assay, lipid peroxidation (LPO) assay, and specific enzymatic assay, respectively.

RESULTS:PL-ES (100µg/mL) exhibited potent anticancer activity, resulting in a significant (40-80%) growth reduction in all 10 cancer cells at 72 hours. PL-I-ES (100 µg/mL) was effective on only four cancer cells but its higher concentration at 250 µg/mL led to a significant (25-90%) growth reduction in seven cancer cells. LPO assays indicated that such a significant growth reduction by PL-ES (100 µg/mL) or PL-I-ES (100 or 250 µg/mL) could result from cell death due to a cytotoxic effect of oxidative stress (through free radicals). Moreover, enzymatic assays for caspase-3 (Csp-3) and caspase-9 (Csp-9), thepro-apoptotic regulators, showed that both enzymes were significantly activated by PL-ES or PL-I-ES, indicating that cell death due to oxidative stress was more likely associated with apoptosis.

CONCLUSIONS:The present study shows that both PL-ES and PL-I-ES indeed have anticancer effects on a variety of cancer cells, although PL-ES appears to be more potent than PL-I-ES. Such an anticancer effect is presumably attributed to oxidative stress, which will ultimately lead to apoptosis. Therefore, these two bioactive mushroom extracts may have clinical implications in a more effective therapeutic option for a variety of human malignancies.

Cancer is the second leading cause of death in the United States with 1.7 million new cases estimated to be diagnosed in 2016. This disease remains a formidable clinical challenge and represents a substantial financial burden to the US health care system. Therefore, research and development of novel therapeutics for the treatment of cancer is of high priority. Cannabinoids and their derivatives have been utilized for their medicinal and therapeutic properties throughout history. Cannabinoid activity is regulated by the endocannabinoid system (ECS), which is comprised of cannabinoid receptors, transporters, and enzymes involved in cannabinoid synthesis and breakdown. More recently, cannabinoids have gained special attention for their role in cancer cell proliferation and death. However, many studies investigated these effects using in vitro models which may not adequately mimic tumor growth and metastasis. As such, this article aims to review study results which evaluated effects of cannabinoids from plant, synthetic and endogenous origins on cancer development in preclinical animal models and to examine the current standing of cannabinoids that are being tested in human cancer patients.

BACKGROUND:Radiotherapy may lead to side effects that undermine patients' quality of life (QOL). Although mind-body practices like qigong appear to improve QOL in cancer survivors, little is known about their benefits for patients who are receiving radiotherapy. Thus, in the current randomized controlled trial, the authors examined the efficacy of a qigong intervention on QOL in women with breast cancer during and after treatment.

METHODS:Ninety-six women with breast cancer were recruited from a cancer center in Shanghai, China, and were randomized to a qigong group (N = 49) or a waitlist control group (N = 47). Women in the qigong group attended 5 weekly classes over 5 or 6 weeks of radiotherapy. QOL outcomes (ie, depressive symptoms, fatigue, sleep disturbance, and overall QOL) and cortisol slopes were assessed at baseline, during treatment, at the end of treatment, 1 month later, and 3 months later.

RESULTS:The mean age of the women was 46 years (range, 25-64 years). Seven percent of women had stage 0 disease, 25% had stage I disease, 40% had stage II disease, and 28% had stage III disease. Fifty-four percent of women underwent mastectomy. Multilevel analyses revealed that women in the qigong group reported less depressive symptoms over time than women in the control group (P = .05). Women who had elevated depressive symptoms at the start of radiotherapy reported less fatigue (P<.01) and better overall QOL (P<.05) in the qigong group compared with the control group, and these findings were clinically significant. No significant differences were observed for sleep disturbance or cortisol slopes.

CONCLUSIONS:The current results indicated that qigong may have therapeutic effects in the management of QOL among women who are receiving radiotherapy for breast cancer. Benefits were particularly evident for patients who had preintervention elevated levels of depressive symptoms.

OBJECTIVE:The objective of this study is to examine the effect of a cognitive, behavioral stress management module of Sudarshan Kriya (SK) and P on levels of serum cortisol and pain among the women suffering from advanced stage breast cancer.

MATERIALS AND METHODS:Participants (n = 147) were screened and randomized to receive standard care (n = 69) versus standard along with SK and Pranayam (P) intervention (n = 78) imparted in one 18 hrs workshop spread during 3 days. Participants were expected to practice it at home 20 min daily as adjuvant to standard pharmacological treatment for pain.

RESULTS:There was a significant difference in blood cortisol levels after 3 months of practice of SK and P. Mean blood levels in the intervention arm were 341.2 ng/ml against 549.2 ng/ml in the control arm (P≤ 0.002). Pain perception in comparison to control arm reduced by 3 points in SK and P arm on 0-10 verbal scale of pain.

CONCLUSION:SK and P is an effective intervention in reducing stress and pain among advance stage patients of breast cancer.

OBJECTIVE:The objective of this study is to examine the effect of a cognitive, behavioral stress management module of Sudarshan Kriya (SK) and P on levels of serum cortisol and pain among the women suffering from advanced stage breast cancer.

MATERIALS AND METHODS:Participants (n = 147) were screened and randomized to receive standard care (n = 69) versus standard along with SK and Pranayam (P) intervention (n = 78) imparted in one 18 hrs workshop spread during 3 days. Participants were expected to practice it at home 20 min daily as adjuvant to standard pharmacological treatment for pain.

RESULTS:There was a significant difference in blood cortisol levels after 3 months of practice of SK and P. Mean blood levels in the intervention arm were 341.2 ng/ml against 549.2 ng/ml in the control arm (P≤ 0.002). Pain perception in comparison to control arm reduced by 3 points in SK and P arm on 0-10 verbal scale of pain.

CONCLUSION:SK and P is an effective intervention in reducing stress and pain among advance stage patients of breast cancer.

BACKGROUND:Many breast cancer survivors experience fatigue, mood, and sleep disturbances.

PURPOSE:This study aims to compare a meditative movement practice, Qigong/Tai Chi Easy (QG/TCE) with sham Qigong (SQG), testing effects of meditation/breath aspects of QG/TCE on breast cancer survivors' persistent fatigue and other symptoms.

METHODS:This double-blind, randomized controlled trial tested 12 weeks of QG/TCE versus SQG on fatigue, depression, and sleep among 87 postmenopausal, fatigued breast cancer survivors, stages 0-III, age 40-75.

RESULTS:Fatigue decreased significantly in the QG/TCE group compared to control at post-intervention (p = 0.005) and 3 months follow-up (p = 0.024), but not depression and sleep quality. Improvement occurred over time for both interventions in depression and sleep quality (all p < 0.05).

CONCLUSIONS:QG/TCE showed significant improvement over time compared to SQG for fatigue, but not depression or sleep. Both QG/TCE and SQG showed improvement for two prevalent symptoms among breast cancer survivors, depression and sleep dysfunction.

Evidence from numerous observational and clinical studies suggest that polyphenolic phytochemicals such as phenolic acids in olive oil, flavonols in tea, chocolate and grapes, and isoflavones in soy products reduce the risk of breast cancer. A dietary food pattern naturally rich in polyphenols is the Mediterranean diet and evidence suggests those of Mediterranean descent have a lower breast cancer incidence. Whilst dietary polyphenols have been the subject of breast cancer risk-reduction, this review will focus on the clinical effects of polyphenols on reducing recurrence. Overall, we recommend breast cancer patients consume a diet naturally high in flavonol polyphenols including tea, vegetables (onion, broccoli), and fruit (apples, citrus). At least five servings of vegetables and fruit daily appear protective. Moderate soy protein consumption (5-10 g daily) and the Mediterranean dietary pattern show the most promise for breast cancer patients. In this review, we present an overview of clinical trials on supplementary polyphenols of dietary patterns rich in polyphenols on breast cancer recurrence, mechanistic data, and novel delivery systems currently being researched.

Since it was discovered that UV radiation was the main environmental cause of skin cancer, primary prevention programs have been started. These programs advise to avoid exposure to sunlight. However, the question arises whether sun-shunning behaviour might have an effect on general health. During the last decades new favourable associations between sunlight and disease have been discovered. There is growing observational and experimental evidence that regular exposure to sunlight contributes to the prevention of colon-, breast-, prostate cancer, non-Hodgkin lymphoma, multiple sclerosis, hypertension and diabetes. Initially, these beneficial effects were ascribed to vitamin D. Recently it became evident that immunomodulation, the formation of nitric oxide, melatonin, serotonin, and the effect of (sun)light on circadian clocks, are involved as well. In Europe (above 50 degrees north latitude), the risk of skin cancer (particularly melanoma) is mainly caused by an intermittent pattern of exposure, while regular exposure confers a relatively low risk. The available data on the negative and positive effects of sun exposure are discussed. Considering these data we hypothesize that regular sun exposure benefits health.

Fatigue is a common, often debilitating, side effect of cancer chemotherapy. Pharmacologic vitamin C has been used as an alternative treatment for the disease itself but its effects on fatigue have not often been documented. Here we report on the case of a woman with recurrent breast cancer, undergoing weekly chemotherapy, with lethargy as a major symptom. Vitamin C (50 g/session) was administered twice weekly and quality of life and multidimensional fatigue symptomology questionnaires were undertaken. Dramatic decreases in fatigue and insomnia were observed, as well as increased cognitive functioning. There were no adverse side effects of i.v. vitamin C.

The aim of this study was to investigate the inhibition of daidzein or/and regular exercise on breast cancer and to reveal the potential biological mechanisms. BALB/c mice pretreated with regular exercise training for 20 days (15 m/min, 60 min/d) were orthotopically transplanted with mouse breast cancer cells (4T1), and then treated with daidzein (145 mg/kg) by gavage for another 22 days. Results showed that exercise or daidzein inhibited tumor growth in mice to a different degree. Particularly, co-treatment with exercise and daidzein showed an obviously synergistic inhibition on the tumor growth (P < 0.01), compared with the tumor control. Further researches indicated that the combination of exercise and daidzein synergistically mobilized and redistributed natural killer cells through upregulating the level of epinephrine and interleukin-6. Moreover, exercise combined with daidzein induces apoptosis in cancer cells via Fas/FasL-initiated mitochondrial apoptosis signaling pathway. These results suggested that regular exercise combined with daidzein may explore a candidate way to prevent and treat the breast cancer.

Topotecan, a derivative of camptothecin, is an important anticancer drug for the treatment of various human cancers in the clinic. While the principal mechanism of tumor cell killing by topotecan is due to its interactions with topoisomerase I, other mechanisms, e.g., oxidative stress induced by reactive free radicals, have also been proposed. However, very little is known about how topotecan induces free radical-dependent oxidative stress in tumor cells. In this report we describe the formation of a topotecan radical, catalyzed by a peroxidase-hydrogen peroxide system. While this topotecan radical did not undergo oxidation-reduction with molecular O2, it rapidly reacted with reduced glutathione and cysteine, regenerating topotecan and forming the corresponding glutathiyl and cysteinyl radicals. Ascorbic acid, which produces hydrogen peroxide in tumor cells, significantly increased topotecan cytotoxicity in MCF-7 tumor cells. The presence of ascorbic acid also increased both topoisomerase I-dependent topotecan-induced DNA cleavage complex formation and topotecan-induced DNA double-strand breaks, suggesting that ascorbic acid participated in enhancing DNA damage induced by topotecan and that the enhanced DNA damage is responsible for the synergistic interactions of topotecan and ascorbic acid. Cell death by topotecan and the combination of topotecan and ascorbic acid was predominantly due to necrosis of MCF-7 breast tumor cells.

Objective. Tai Chi Chuan (TCC) is a form of aerobic exercise that may be an effective therapy for improving psychosomatic capacity among breast cancer survivors. This meta-analysis analyzed the available randomized controlled trials (RCTs) on the effects of TCC in relieving treatment-related side effects and quality of life in women with breast cancer. Methods. RCTs were searched in PubMed, Embase, Web of Science, and Cochrane Library through April 2014. Data were analyzed on pathology (pain, interleukin-6, and insulin-like growth factor 1), physical capacity (handgrip, limb physical fitness, and BMI), and well-being (physical, social, emotional, and general quality of life). Results. Nine RCTs, including a total of 322 breast cancer patients, were examined. Compared with control therapies, the pooled results suggested that TCC showed significant effects in improving handgrip dynamometer strength, limb elbow flexion (elbow extension, abduction, and horizontal adduction). No significant differences were observed in pain, interleukin-6, insulin-like growth factor, BMI, physical well-being, social or emotional well-being, or general health-related quality of life. Conclusion. The short-term effects of TCC may have potential benefits in upper limb functional mobility in patients with breast cancer. Additional randomized controlled trials with longer follow-up are needed to provide more reliable evidence.

INTRODUCTION:Recent reports have suggested that breast ultrasound (US) is of value in distinguishing malignant from benign processes. The aim of this study was to establish the accuracy of US in detecting invasive malignancy in clinically benign, discrete, symptomatic breast lumps.

METHODS:The US appearances of 205 clinically benign breast masses were documented prospectively and prior to mammography by one radiologist (AJE). The US appearances were then correlated with the fine needle aspiration (FNA), core biopsy and surgical findings and compared with the mammographic findings.

RESULTS:The US findings were normal 72 (35%), simple cyst 63 (31%), solid benign 51 (25%), solid indeterminate 15 (7%) and solid malignant four (2%). Ultrasound characterized 13 (93%) of the 14 patients found to have invasive carcinoma as indeterminate or malignant. No patients with normal or simple cyst US findings had invasive malignancy. Ultrasound had significantly better accuracy (97% vs 87%, P<0.02) sensitivity (93% vs 57%, P<0.05) and negative predictive value (99% vs 92%, P<0.002) than mammography in the detection of invasive carcinoma when indeterminate and malignant imaging findings were taken as positive.

CONCLUSION:US is a useful adjunct to FNA/core biopsy in confirming the nature of symptomatic, clinically benign breast masses and is superior to mammography in this clinical setting.

Problems with attention and symptom distress are common clinical features reported by women who receive adjuvant chemotherapy for breast cancer. Mindfulness practice significantly improves attention and mindfulness programs significantly reduce symptom distress in patients with cancer, and, more specifically, in women with breast cancer. Recently, a pilot investigation of a music therapy program, built on core attitudes of mindfulness practice, reported significant benefits of enhanced attention and decreased negative mood and fatigue in women with breast cancer. This paper delineates the design and development of the mindfulness-based music therapy (MBMT) program implemented in that pilot study and includes clients' narrative journal responses. Conclusions and recommendations, including recommendation for further exploration of the function of music in mindfulness practice are provided.

Problems with attention and symptom distress are common clinical features reported by women who receive adjuvant chemotherapy for breast cancer. Mindfulness practice significantly improves attention and mindfulness programs significantly reduce symptom distress in patients with cancer, and, more specifically, in women with breast cancer. Recently, a pilot investigation of a music therapy program, built on core attitudes of mindfulness practice, reported significant benefits of enhanced attention and decreased negative mood and fatigue in women with breast cancer. This paper delineates the design and development of the mindfulness-based music therapy (MBMT) program implemented in that pilot study and includes clients' narrative journal responses. Conclusions and recommendations, including recommendation for further exploration of the function of music in mindfulness practice are provided.

The purpose of this randomized controlled trial was to determine the effects of resistance training (RT) on markers of inflammation and immune function in breast cancer survivors. Thirty-nine breast cancer survivors were randomly assigned to a RT (n = 20) or control (n = 19) group. RT performed supervized exercise three times per week. Natural killer cell (NK) and natural killer T-cell (NKT) function, and markers of inflammation (serum TNF-α, IL-6, IL-10, and CRP) were measured before and after training. Changes in NK and NKT cell function were analyzed using ANCOVA, with the change score the dependent variable, and the baseline value of the same variable the covariate. Effect sizes (ES) were calculated via partial eta-squared. We found a significant reduction, and large associated ESs, in the RT group compared to the control groupfor change in NK cell expression of TNF-α (p = 0.005, ES = 0.21) and NKT cell expression of TNF-α (p = 0.04, ES = 0.12). No differences were observed in any serum marker. Significant improvements in all measurements of strength were found in RT compared to control (p < 0.001; large ESs ranging from 0.32 to 0.51). These data demonstrate that RT has a beneficial effect on the NK and NKT cell expression of TNF-α indicating that RT may be beneficial in improving the inflammatory profile in breast cancer survivors.

This pilot study examined the effects of Reiki therapy and companionship on improvements in quality of life, mood, and symptom distress during chemotherapy. Thirty-six breast cancer patients received usual care, Reiki, or a companion during chemotherapy. First, data were collected from patients receiving usual care. Second, patients were randomized to either receive Reiki or a companion during chemotherapy. Questionnaires assessing quality of life, mood, symptom distress, and Reiki acceptability were completed at baseline and chemotherapy sessions 1, 2, and 4. Reiki was rated relaxing with no side effects. Reiki and companion groups reported improvements in quality of life and mood that were greater than those seen in the usual care group. Interventions during chemotherapy, such as Reiki or companionship, are feasible, acceptable, and may reduce side effects.

BACKGROUND:Preclinical evidence shows that short-term fasting (STF) protects healthy cells against side effects of chemotherapy and makes cancer cells more vulnerable to it. This pilot study examines the feasibility of STF and its effects on tolerance of chemotherapy in a homogeneous patient group with early breast cancer (BC).

METHODS:Eligible patients had HER2-negative, stage II/III BC. Women receiving (neo)-adjuvant TAC (docetaxel/doxorubicin/cyclophosphamide) were randomized to fast 24 h before and after commencing chemotherapy, or to eat according to the guidelines for healthy nutrition. Toxicity in the two groups was compared. Chemotherapy-induced DNA damage in peripheral blood mononuclear cells (PBMCs) was quantified by the level ofγ-H2AX analyzed by flow cytometry.

RESULTS:Thirteen patients were included of whom seven were randomized to the STF arm. STF was well tolerated. Mean erythrocyte- and thrombocyte counts 7 days post-chemotherapy were significantly higher (P = 0.007, 95 % CI 0.106-0.638 and P = 0.00007, 95 % CI 38.7-104, respectively) in the STF group compared to the non-STF group. Non-hematological toxicity did not differ between the groups. Levels ofγ-H2AX were significantly increased 30 min post-chemotherapy in CD45 + CD3- cells in non-STF, but not in STF patients.

CONCLUSIONS:STF during chemotherapy was well tolerated and reduced hematological toxicity of TAC in HER2-negative BC patients. Moreover, STF may reduce a transient increase in, and/or induce a faster recovery of DNA damage in PBMCs after chemotherapy. Larger studies, investigating a longer fasting period, are required to generate more insight into the possible benefits of STF during chemotherapy.

TRIAL REGISTRATION:ClinicalTrials.gov: NCT01304251 , March 2011.

OBJECTIVES:Previous research has found that yoga can enhance quality of life and ease menopausal symptoms of breast cancer survivors. The study examined whether self-esteem mediated the effects of yoga on quality of life, fatigue and menopausal symptoms, utilizing validated outcome measures.

STUDY DESIGN:This is a secondary analysis of a randomized controlled trial comparing the effects of yoga with those of usual care in 40 breast cancer survivors who suffered from menopausal symptoms. All participants completed all 3 assessments (week 0, week 12, and week 24) and provided full data.

MAIN OUTCOME MEASURES:Outcomes were measured using self-rating instruments. Mediation analyses were performed using SPSS.

RESULTS:Self-esteem mediated the effect of yoga on total menopausal symptoms (B=-2.11, 95% BCI [-5.40 to -0.37]), psychological menopausal symptoms (B=-0.94, 95% BCI [-2.30 to -0.01]), and urogenital menopausal symptoms (B=-0.66, 95% BCI [-1.65 to -0.15]), quality of life (B=8.04, 95% BCI [3.15-17.03]), social well-being (B=1.80, 95% BCI [0.54-4.21]), emotional well-being (B=1.62, 95% BCI [0.70-3.34]), functional well-being (B=1.84, 95% BCI [0.59-4.13]), and fatigue (B=4.34, 95% BCI [1.28-9.55]). Self-esteem had no effect on somatovegetative menopausal symptoms (B=-0.50, 95% BCI n.s.) or on physical well-being (B=0.79, 95% BCI n.s.).

CONCLUSIONS:Findings support the assumption that self-esteem plays a vital role in the beneficial effect of yoga and that yoga can have long-term benefits for women diagnosed with breast cancer and undergoing menopausal transition.