Positive affect and fatigue as predictors of anti-inflammatory IL-10 concentrations among colorectal cancer patients during adjuvant chemotherapy.

OBJECTIVES: (1) To examine the relationships of positive and negative affect and symptoms of depression, anxiety, and fatigue at baseline with the anti-inflammatory cytokine IL-10 concentrations in serum at three points in colorectal cancer patients; and (2) to assess the relationship between these factors and disease recurrence or mortality after a median follow-up of 24 months. METHODS: In a prospective trial, 92 stage II or III colorectal cancer patients scheduled to receive standard chemotherapy were enrolled. Blood samples were collected prior to start of chemotherapy onset (T0), 3 months later (T1), and upon chemotherapy completion (T2). RESULTS: IL-10 concentrations were similar across the time points. Linear mixed-effects model analysis showed that controlling for confounders, higher positive affect and lower fatigue pretreatment (T0) predicted IL-10 concentrations across the time points (estimate = 0.18, SE = 0.08, 95% CI = 0.03, 0.34, p < .04 and estimate = -0.25, SE = 0.12, 95% CI = -0.50, 0.01, p < .04, respectively). Depression at T0 significantly predicted higher disease recurrence and mortality (estimate = 0.17, SE = 0.08, adjusted OR = 1.18, 95% CI = 1.02, 1.38, p = .03). CONCLUSIONS: We report on associations not previously assessed between positive affect and fatigue and the anti-inflammatory cytokine IL-10. Results add to previous findings suggesting that positive affect and fatigue could have a role in anti-inflammatory cytokine dysregulation.

Circulating blood extracellular vesicles as a tool to assess endothelial injury and chemotherapy toxicity in adjuvant cancer patients.

Extracellular vesicles (EVs) are subcellular membrane blebs that include exosomes and microparticles, which represent a potential source for cancer biomarker discovery. We assess EVs characteristics as a tool to evaluate the endothelial and anti-tumor treatment injury during adjuvant chemotherapy in breast (BC) and colon cancer (CC) patients. Blood samples were taken from 29 BC and 25 CC patients before and after chemotherapy, as well as from healthy control donors (HC). Circulating blood EVs were isolated and characterized by size/concentration, membrane antigens for cell origin, thrombogenicity, and protein content. We observed higher EVs concentration and particle size in CC patients after chemotherapy compared with HC. Higher levels of endothelial EVs (CD144-positive) and vascular endothelial growth factor receptor 1 (VEGFR1), apparently as an indication of endothelial dysfunction, were found in all cancer patients, regardless of a given treatment, compared to HC. Levels of EVs labeled CD62E, CD34+41-, the lymphocyte markers CD11+ and CD-14+, Annexin-V, and the coagulation proteins TF and TFPI, however, sometimes demonstrate significant differences between patients, although HC did not show significant differences between patients pre- and post-chemotherapy. Most importantly, increasing levels of EVs encapsulated Angiostatin were found in patients with CC, while chemotherapy treatment leads to its notable rise in circulating blood EVs. Our results demonstrate the potential of EVs encapsulated Angiostatin as a tool to evaluate endothelial damage during adjuvant chemotherapy in BC and CC patients.

Extracellular Vesicles Reflect the Efficacy of Wheatgrass Juice Supplement in Colon Cancer Patients During Adjuvant Chemotherapy.

INTRODUCTION: Colorectal cancer (CC) is the third most common type of cancer, accounting for 10% of all cancer cases. Adjuvant chemotherapy is recommended in stages II-III CC. Wheatgrass juice (WGJ) from wheat seeds has high nutritional values, may induce synergistic benefits to chemotherapy and may attenuate chemotherapy-related side effects. Extracellular vesicles (EVs) are subcellular membrane blebs. EVs include exosomes (generated in the endosome, in size <150 nm) and microvesicles (shed from the plasma cell membrane) provide information on their parental cells and play a role in intercellular communication. We aimed to elucidate the effects of chemotherapy administration with supportive treatment of WGJ on CC patients' EVs characteristics. METHODS: EVs were isolated from the blood samples of 15 healthy controls (HCs) and 50 CC patients post-surgery, treated by chemotherapy, with or without additional daily WGJ. Blood samples were taken before, during, and at the end of chemotherapy. EVs were characterized by size, concentration, membrane antigens and cytokine content using nanoparticle-tracking analysis, western blot, flow cytometry, and protein array methods. RESULTS: EVs were found to be similar by size and concentration with reduced levels of exosome markers (CD81) on samples at the end of combined treatment (chemotherapy and WGJ). Higher levels of endothelial EVs, which may indicate impairment of the vascular endothelial cells during treatment, were found in CC patients treated by chemotherapy only compared to those with chemotherapy and daily WGJ. Also, EVs thrombogenicity was lower in patients added WGJ compared to patients who had only chemotherapy (levels of tissue factor p = 0.029 and endothelial protein C receptor p = 0.005). Following treatments, levels of vascular endothelial growth factor receptors (VEGFR-1) and the majority of growth-factors/pro-inflammatory cytokines were higher in EVs of patients treated by chemotherapy only than in EVs obtained from patients with the combined treatment. CONCLUSION: Daily consumption of WGJ during chemotherapy may reduce vascular damage and chemotherapy-related thrombogenicity, growth factors and cytokines, as reflected by the characteristics of patient's EVs.

Wheatgrass Juice Administration and Immune Measures during Adjuvant Chemotherapy in Colon Cancer Patients: Preliminary Results.

Adjuvant chemotherapy is recommended in high-risk stage II-III colorectal cancer (CC). We examine the effect of daily wheatgrass juice (WGJ) intake in addition to chemotherapy on immune parameters, including IL-6, IL-8, IL-10, IL-12, and white blood cells (WBCs) among CC patients. In a controlled prospective trial, 100 stage II-III CC patients were enrolled. According to patient preference, they were divided into two subgroups, control group and intervention group, 50 patients each, all of whom received the same standard postoperative adjuvant chemotherapy, plus consumption of 60 cc WGJ daily in the intervention group. Blood samples were collected at baseline (T0) and upon treatment termination, 5-6 months later (T1). Cytokine concentrations were assessed using ELISA kits. Anti-inflammatory cytokine IL-10 concentrations were significantly higher in the WGJ group than in the control group at T1. The decline in WBC counts between T0 and T1 was significantly lower in the WGJ group. No significant differences were observed in IL-6, IL-8, and IL-12 concentrations between the study groups. The higher levels of IL-10 and the attenuating of WBC decline during chemotherapy may constitute preliminary evidence of the beneficial effects of WGJ on immune parameters, when given as a supplement to standard care. In light of these preliminary results, WGJ supports immunological parameters during adjuvant chemotherapy. Nevertheless, future studies are needed in order to translate those results to clinical recommendations for cancer survivors.

Is the clinical use of cannabis by oncology patients advisable?

The use of the cannabis plant for various medical indications by cancer patients has been rising significantly in the past few years in several European countries, the US and Israel. The increase in use comes from public demand for the most part, and not due to a scientific basis. Cannabis chemistry is complex, and the isolation and extraction of the active ingredient remain difficult. The active agent in cannabis is unique among psychoactive plant materials, as it contains no nitrogen and, thus, is not an alkaloid. Alongside inconclusive evidence of increased risks of lung and head and neck cancers from prolonged smoking of the plant produce, laboratory evidence of the anti-cancer effects of plant components exists, but with no clinical research in this direction. The beneficial effects of treatment with the plant, or treatment with medicine produced from its components, are related to symptoms of the disease: pain, nausea and vomiting, loss of appetite and weight loss. The clinical evidence of the efficacy of cannabis for these indications is only partial. However, recent scientific data from studies with THC and cannabidiol combinations report the first clinical indication of cancer-related pain relief. The difficulties of performing research into products that are not medicinal, such as cannabis, have not allowed a true study of the cannabis plant extract although, from the public point of view, such studies are greatly desirable.

Chemotherapy-related cognitive impairment: does integrating complementary medicine have something to add? Review of the literature.

Chemotherapy-related cognitive impairment is a phenomenon of cognitive decline that some patients experience during and after chemotherapy. The prevalence of chemotherapy-related cognitive impairment in cancer survivors ranges from 14 to 85 %. Memory loss and lack of concentration are the most frequent symptoms, often resulting in deterioration of daily functioning and a decreased quality of life. Despite ongoing research on chemotherapy-related cognitive impairment, a clear understanding of the underlying mechanisms of the neurotoxicity induced by chemotherapy and the factors that determine a patient's vulnerability are still lacking. We review current knowledge regarding the etiology of chemotherapy-related cognitive impairment, risk factors, conventional therapy, coping strategies, and potential complementary and integrative medicine treatments. Complementary and integrative medicine modalities that may improve chemotherapy-related cognitive impairment include mind-body techniques and acupuncture, as well as nutrition and herbal therapies. Studies on these modalities have not directly tested the hypothesis of modifying chemotherapy-related cognitive impairment and were done on different disorders of memory loss and lack of concentration. We recommend conducting further research on the potential role of complementary and integrative medicine modalities in the treatment and prevention of chemotherapy-related cognitive impairment.