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Background: Standardized chemotherapy for breast cancer can improve the survival of patients, but during the process, it is accompanied by a variety of symptoms., Objective: To explore the dynamic changes of symptoms and quality of life in breast cancer patients at different time points during chemotherapy, and to explore the correlation with quality of life., Method: A prospective study method was used to collect 120 breast cancer patients undergoing chemotherapy as the research objects. The general information questionnaire, the Chinese version of the M.D. Anderson Symptom inventory (MDASI-C), and the European Organization for Cancer Research and Treatment (EORTC) Quality of Life questionnaire were used in the first week (T1), first month (T2), three month (T3) and 6 months after chemotherapy (T4) to conduct dynamic investigation., Results: The symptoms of breast cancer patients at four time points during chemotherapy period were: psychological symptoms, pain-related symptoms, perimenopausal symptoms, impaired self-image, and neurological related symptoms etc. At T1, it exhibited 2 symptoms, however as moving along the chemotherapy process, the symptoms are increasing. The severity is (F= 76.32, P< 0.001), life of quality (F= 117.64, P< 0.001) vary. At T3, there were 5 symptoms, and at T4 symptom number increased to 6 with worsening quality of life. It exhibited positive correlation with scores in multiple domains of quality of life (P< 0.05), and the above symptoms showed positive correlation with multiple domains of QLQ-C30 (P< 0.05)., Conclusion: After T1-T3 of chemotherapy in breast cancer patients, the symptoms become more serious and the quality of life reduced. Therefore, medical staff should pay attention to the occurrence and development of patient's symptoms, create a reasonable plan from the perspective of symptom management and carry out personalized interventions to improve patient's quality of life.

Background: Nausea and vomiting are the most common complications following chemotherapy and usually lead to decreased quality of life. Acupuncture therapy is an effective method for chemotherapy-induced nausea and vomiting (CINV), the effects and safety have been observed by many clinicians and demonstrated in a systematic review, which was included in the Cochrane Library in 2014. After several years, new studies have occurred and an updated systematic evaluation is needed. This protocol describes a method for performing a systematic review and meta-analysis to further evaluate the beneficial effects and safety of acupuncture for CINV., Methods: A searching strategy will be carried out mainly in eight databases in English and Chinese, Cochrane Central Register of Controlled Trials, PubMed, Embase, China National Knowledge Infrastructure, the Chinese Scientific Journal Database, the Wanfang database, China Doctoral Dissertations Full-text Database, and China Master's Theses Full-text Database. Only randomized controlled trials related to acupuncture for CINV will be included to enhance the effectiveness. The effective percentage will be used as primary outcome. Changes in the symptoms of nausea and vomiting, like severity, duration, and frequency as well as quality of life will be assessed as secondary outcome. Side effects and adverse events will be used as safety evaluations. To ensure the quality of the systematic evaluation, study selection, data extraction, and quality assessment will be independently performed by 2 authors, and the third author will deal with any disagreement. The Review Manager V.5.3.3 s will be used to perform the data synthesis and subgroup analysis., Results: There are additional studies, further explanations and more subgroup analyses compared with the previous systematic analysis to determine the effects and safety of acupuncture for CINV., Conclusion: The result of this systematic review may offer clinicians stronger evidence to assist patient in relieving CINV., Ethics and Dissemination: There is no need to acquire ethical approval for individuals come from literatures instead of recruiting directly. The findings of this review will be reported in peer-reviewed publications and/or presented at relevant conferences TRIAL REGISTRATION NUMBER:: CRD42016045223.

Gambogic acid (GA) is a potential anti-cancer compound that is extracted from the resin of Garciania hanburyi. The present study was designed to evaluate the anti-metastatic effect of GA on melanoma cell lines in vitro and to explore the underlying mechanism. The anti-proliferative activity of GA on melanoma cells was assessed by CCK-8 assay. The Wound-healing, transwell, adhesion, and tube formation assays were performed to examine the inhibition of GA on the cell's migration, invasion, adhesion, and angiogenesis capacities, respectively. Enzymatic activity of MMP-2 and MMP-9 were detected by gelatin zymography assay. Protein expressions regulated by GA treatment were tested by Western blot assay. The present results showed that GA significantly inhibited the proliferation of highly metastatic melanoma A375, B16-F10 cells and human umbilical vein endothelial cells (HUVECs) in time- and doses-dependent manners. Furthermore, GA significantly inhibited the migratory, invasive and adhesive properties of A375 and B16-F10 cells, and tube-forming potential of HUVECs at sub-IC 50 concentrations, where no significant cytotoxicity was observed. Mechanistically, GA treatment suppressed the EMT and angiogenesis processes and reduced the enzymatic activity of MMP-2 and MMP-9. Moreover, abnormal PI3K/Akt and ERK signaling pathways in A375 and B16-F10 cells and HUVECs were notably suppressed by GA treatment. Collectively, our results suggest that GA exerts anti-metastasis activity in melanoma cells by suppressing the EMT and angiogenesis through the PI3K/Akt and ERK signaling pathways, and might be used as a phytomedicine against metastatic melanoma., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Chemotherapy-induced cognitive impairment, also known as "chemobrain," is a common side effect. The purpose of this study was to examine whether ginsenoside Rg1, a ginseng-derived compound, could prevent chemobrain and its underlying mechanisms. A mouse model of chemobrain was developed with three injections of docetaxel, adriamycin, and cyclophosphamide (DAC) in combination at a 2-day interval. Rg1 (5 and 10 mg/kg daily) was given 1 week prior to DAC regimen for 3 weeks. An amount of 10 mg/kg Rg1 significantly improved chemobrain-like behavior in water maze test. In vivo neuroimaging revealed that Rg1 co-treatment reversed DAC-induced decreases in prefrontal and hippocampal neuronal activity and ameliorated cortical neuronal dendritic spine elimination. It normalized DAC-caused abnormalities in the expression of multiple neuroplasticity biomarkers in the two brain regions. Rg1 suppressed DAC-induced elevation of the proinflammatory cytokines tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6), but increased levels of the anti-inflammatory cytokines IL-4 and IL-10 in multiple sera and brain tissues. Rg1 also modulated cytokine mediators and inhibited DAC-induced microglial polarization from M2 to M1 phenotypes. In in vitro experiments, while impaired viability of PC12 neuroblastic cells and hyperactivation of BV-2 microglial cells, a model of neuroinflammation, were observed in the presence of DAC, Rg1 co-treatment strikingly reduced DAC's neurotoxic effects and neuroinflammatory response. These results indicate that Rg1 exerts its anti-chemobrain effect in an association with the inhibition of neuroinflammation by modulating microglia-mediated cytokines and the related upstream mediators, protecting neuronal activity and promoting neuroplasticity in particular brain regions associated with cognition processing.

Chemotherapy-induced cognitive impairment, often referred to as "chemobrain," is a common side effect. In this study, mice received three intraperitoneal injections of a combination of docetaxel, adriamycin, and cyclophosphamide (DAC) at 2-day intervals. A water maze test was used to examine cognitive performance, and manganese-enhanced magnetic resonance imaging (MEMRI) was used to examine hippocampal neuronal activity. The whole brain, prefrontal cortex, hippocampus, and blood samples were then collected for cytokine measurement. The DAC-treated mice displayed a significantly shorter duration spent in and fewer entries into the target quadrant of the water maze than the control mice and a pronounced decrease in MEMRI signal intensity in the hippocampal subregions. In a separate experiment using in vivo transcranial two-photon imaging, DAC markedly eliminated dendritic spines without changing the rate of spine formation, leading to a striking loss of spines in the medial prefrontal cortex. DAC treatment resulted in significant elevations in the levels of the proinflammatory cytokines interleukin 6 (IL-6) and tumor necrosis factor-α (TNF-α) and in significant decreases in the levels of the anti-inflammatory cytokines IL-4 and IL-10 in most of the sera and brain tissues examined. The IL-6 and TNF-α levels of several sera and brain tissues showed strong inverse correlations with the duration and number of entries in the target quadrant of the water maze and with the hippocampal MEMRI signal intensity, but also showed striking positive correlations with spine elimination and loss. These results indicate that chemobrain is associated with cytokine dysregulation and disrupted neuroplasticity of the brain.

Chemotherapy-induced cognitive impairment, also known as "chemobrain," is a common side effect. The purpose of this study was to examine whether resveratrol, a natural polyphenol that has nootropic effects, could prevent chemobrain and its underlying mechanisms. Mice received three injections of docetaxel, adriamycin, and cyclophosphamide (DAC) in combination, a common chemotherapy regimen, at two-day intervals within one week. Resveratrol (50 and 100 mg/kg per day) was orally administered for three weeks, beginning one week before the DAC treatment. Water maze test and manganese-enhanced magnetic resonance imaging were used to evaluate animals' cognitive performance and brain neuronal activity, respectively. Blood and brain tissues were collected for measurement of cytokines, cytokine regulators, and biomarkers for neuroplasticity. DAC treatment produced a striking cognitive impairment. Cotreatment with 100 mg/kg resveratrol ameliorated DAC-induced cognitive impairment and decreases in prefrontal and hippocampal neuronal activity. Mice co-treated with both doses of resveratrol displayed significantly lower levels of the proinflammatory cytokines tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6), but markedly higher levels of the anti-inflammatory cytokines IL-4 and IL-10 in several sera and brain tissues than those co-treated with vehicle. Resveratrol modulated the cytokine-regulating pathway peroxisome proliferator activated receptor (PPAR)-γ/nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), and protected against DAC-induced decreases in the expression of the neuroplasticity biomarkers, brain-derived neurotrophic factor (BDNF), tropomyosin receptor kinase B (TrkB), amino acid neurotransmitter receptors, and calmodulin-dependent protein kinase II (CaMKII). These results demonstrate the efficacy of resveratrol in preventing chemobrain and its association with cytokine modulation and neuroprotection., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Background: Chemotherapy-induced nausea and vomiting (CINV) is one of the most common and distressing side effects in patients with cancer. The introduction and development of antiemetic drugs have significantly improved the ability of clinicians to control CINV, but it is not easy to translate to practical application, owing to financial issues, provider-related barriers, and patient factors. Nondrug therapies are needed to alleviate the symptoms of CINV. Acupuncture is an appropriate adjunctive treatment for CINV, but additional evidence is needed., Methods/design: This study is a multicenter, randomized, sham-controlled prospective clinical trial. A total of 136 participants will be randomly allocated into the intervention group (verum acupuncture) or the control group (sham acupuncture) in a 1:1 ratio. All treatment will be given for 5 days. Participants in both groups will receive acupuncture sessions twice on the first day of chemotherapy and once consecutively on the following 4 days. Each session takes approximately 30 minutes. The primary outcome measure will be the Common Terminology Criteria for Adverse Events to assess CINV. The secondary outcome measures will be the Eastern Cooperative Oncology Group score, Simplified Nutritional Appetite Questionnaire, and Hospital Anxiety and Depression scale. Safety will be assessed at each visit., Discussion: The results of this trial will provide clinical evidence for the effect and safety of acupuncture for CINV., Trial Registrations: ISRCTN Registry identifier: ISRCTN13287728 ). Registered on 28 February 2015. ClinicalTrials.gov identifier: NCT02369107 . Registered on 17 February 2015.

Cholangiocarcinoma (CCA), a devastating cancer with a poor prognosis, is resistant to the currently available chemotherapeutic agents. Capsaicin, the major pungent ingredient found in hot red chili peppers of the genus Capsicum, suppresses the growth of several malignant cell lines. Our aims were to investigate the role and mechanism of capsaicin with respect to the sensitivity of CCA cells to chemotherapeutic agents. The effect of capsaicin on CCA tumor sensitivity to 5-fluorouracil (5-FU) was assessed in vitro in CCA cells and in vivo in a xenograft model. The drug sensitivity of QBC939 to 5-FU was significantly enhanced by capsaicin compared with either agent alone. In addition, the combination of capsaicin with 5-FU was synergistic, with a combination index (CI) < 1, and the combined treatment also suppressed tumor growth in the CCA xenograft to a greater extent than 5-FU alone. Further investigation revealed that the autophagy induced by 5-FU was inhibited by capsaicin. Moreover, the decrease in AKT and S6 phosphorylation induced by 5-FU was effectively reversed by capsaicin, indicating that capsaicin inhibits 5-FU-induced autophagy by activating the phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT)/mammalian target of rapamycin (mTOR) pathway in CCA cells. Taken together, these results demonstrate that capsaicin may be a useful adjunct therapy to improve chemosensitivity in CCA. This effect likely occurs via PI3K/AKT/mTOR pathway activation, suggesting a promising strategy for the development of combination drugs for CCA.

One consequence of modern cancer therapy is chemotherapy related cognitive dysfunction or "chemobrain", the subjective experience of cognitive deficits at any point during or following chemotherapy. Chemobrain, a well-established clinical syndrome, has become an increasing concern because the number of long-term cancer survivors is growing dramatically. There is strong evidence that correlates changes in peripheral cytokines with the development of chemobrain in commonly used chemotherapeutic drugs for different types of cancer. However, the mechanisms by which these cytokines elicit change in the central nervous system are still unclear. In this review, we hypothesize that the administration of chemotherapy agents initiates a cascade of biological changes, with short-lived alterations in the cytokine milieu inducing persistent epigenetic alterations. These epigenetic changes lead to changes in gene expression, alterations in metabolic activity and neuronal transmission that are responsible for generating the subjective experience of cognition. This speculative but testable hypothesis should help to gain a comprehensive understanding of the mechanism underlying cognitive dysfunction in cancer patients. Such knowledge is critical to identify pharmaceutical targets with the potential to prevent and treat cancer-treatment related cognitive dysfunction and similar disorders., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

To investigate the influence of bear bile on rat hepatocarcinoma induced by diethylnitrosamine (DEN), a total of 40 rats were randomly divided into 4 groups: normal control group, model group, and two bear bile treatment groups. The rat liver cancer model was induced by breeding with water containing 100 mg x L(-1) DEN for 14 weeks. The rats of the bear bile groups received bear bile powder (200 or 400 mg x kg(-1)) orally 5 times per week for 18 weeks. The general condition and the body weight of rats were examined every day. After 18 weeks the activities of serum alanine transaminase (ALT), aspartate transaminase (AST) and total bilirubin (TBIL) were detected. Meanwhile, the pathological changes of liver tissues were observed after H&E staining. The expression of proliferative cell nuclear antigen (PCNA) and a-smooth muscle actin (alpha-SMA) in liver tissue were detected by immunohistochemical method. After 4 weeks the body weights of rats in normal group were significantly more than that in other groups (P < 0.05); and that in the two bile groups was significantly more than that in the model group. Compared with normal group, the level of serum glutamic-pyruvic transaminase and total bilirubin increased significantly in other groups; compared with model group, these two indexes decreased significantly in two bile groups. Hepatocellular carcinoma occurred in all rats except for normal group; there were classic cirrhosis and cancer in model group while there were mild cirrhosis and high differentiation in two bile groups. There were almost no expressions of PCNA and alpha-SMA in normal group while there were high expressions in model group; the two bile groups had some expressions but were inferior to the model group, and alpha-SMA reduced markedly. It indicated that bear bile restrained the development of liver cancer during DEN inducing rat hepatocarcinoma, which may be related to its depressing hepatic stellate cell activation and relieving hepatic lesion and cirrhosis.

Chemotherapy-induced peripheral neuropathy (CIPN), a dose-limiting neurotoxic effect of chemotherapy, is the most common reason for early cessation of cancer treatment. This can result in an increased risk of recurrence and decreased survival rate. Inflammatory cascade activation, proinflammatory cytokine upregulation, and neuro-immune communication pathways play essential roles in the initiation and progression of CIPN. Most notably, TNF-α, IL-1β, IL-6, and CCL2 are involved in neuropathic pain. Further elucidation of the role of these cytokines could lead to their development and use as biomarkers for predicting the onset of painful peripheral neuropathy and early axonal damage. In this review, we provide evidence for the involvement of cytokines in CIPN, the possible underlying mechanisms, and their use as potential therapeutic targets and biomarkers to prevent and improve the painful peripheral neuropathy related to chemotherapeutic agents., (Published by Elsevier Ltd.)

Background: Chemotherapy-induced nausea and vomiting (CINV) is one of the most common and distressing side effects in patients with cancer. The introduction and development of antiemetic drugs have significantly improved the ability of clinicians to control CINV, but it is not easy to translate to practical application, owing to financial issues, provider-related barriers, and patient factors. Nondrug therapies are needed to alleviate the symptoms of CINV. Acupuncture is an appropriate adjunctive treatment for CINV, but additional evidence is needed.Methods/design: This study is a multicenter, randomized, sham-controlled prospective clinical trial. A total of 136 participants will be randomly allocated into the intervention group (verum acupuncture) or the control group (sham acupuncture) in a 1:1 ratio. All treatment will be given for 5 days. Participants in both groups will receive acupuncture sessions twice on the first day of chemotherapy and once consecutively on the following 4 days. Each session takes approximately 30 minutes. The primary outcome measure will be the Common Terminology Criteria for Adverse Events to assess CINV. The secondary outcome measures will be the Eastern Cooperative Oncology Group score, Simplified Nutritional Appetite Questionnaire, and Hospital Anxiety and Depression scale. Safety will be assessed at each visit.Discussion: The results of this trial will provide clinical evidence for the effect and safety of acupuncture for CINV.Trial Registrations: ISRCTN Registry identifier: ISRCTN13287728 ). Registered on 28 February 2015. ClinicalTrials.gov identifier: NCT02369107 . Registered on 17 February 2015. [ABSTRACT FROM AUTHOR]

Six new cadinane-type sesquiterpenoids, named Chimnitensin A-F (1–6) were isolated from the leaves of Chimonanthus nitens Oliv. Their structures were elucidated by comprehensive spectroscopic analyses and comparison with structurally related known analogues. In vitro MTT assay showed that all six compounds had cytotoxicity against two selected human breast cancer cell lines (MDA-MB-468 and MDA-MB-231), which indicate their potential of developing into anticancer drugs. [Display omitted] [ABSTRACT FROM AUTHOR]

Astragalus mongholicus, Solanum nigrum Linn, Lotus plumule, Ligusticum are widely used traditional herbal medicines for cancer treatment in China. They were typical drugs selected from Gubenyiliu II and series of formula (GYII), which were developed on the foundation of YIQIHUOXUEJIEDU theory. In the present study, four active ingredients (Astragaloside IV, α-solanine, neferine, and 2,3,5,6-tetramethylpyrazine) derived from medicines above were applied in combination as SANT. Triple-negative breast cancer (TNBC) is a serious threat to women's health worldwide. Heparanase (HPSE) is often up-regulated in breast cancer with the properties of facilitating tumorigenesis and influencing the autophagy process in cancer cells. This study aimed at evaluating the anti-tumor potential of SANT in treating HPSE related TNBC both in-vitro and in-vivo. In this study, we explored the correlation between HPSE expression and survival of breast cancer patients in databases. We performed MTS, trans-well and wound scratch assays to assess the impact of SANT on cell proliferation and migration. Confocal microscopy observation and western blots were applied to verify the autophagy flux induced by SANT. Mice models were employed to evaluate the efficacy and safety of SANT in-vivo by tumor weights and volumes or serum index, respectively. To analyze the underlying mechanisms of SANT, we conducted human autophagy PCR array and angiogenesis proteome profiler on tumor tissues. Patients with elevated HPSE expression were associated with a poor outcome in both RFS (P = 1.7e-12) and OS (P = 0.00016). SANT administration significantly inhibited cancer cells' proliferation and migration, enhanced autophagy flux, and slightly reduced the active form of HPSE in-vitro. SANT also suppressed tumor growth and angiogenesis in-vivo. Human autophagy PCR array results indicated that SANT increased the ATG16L1, ATG9B, ATG4D gene expressions while decreased TMEM74 and TNF gene expressions.Angiogenesis proteome profiler results showed SANT reduced protein level of HB-EGF, thrombospondin-2, amphiregulin, leptin, IGFBP-9, EGF, coagulation factor III, and MMP-9 (pro and active form) in tumor, raised the protein expression of serpin E1 and platelet factor 4. These findings indicated that herbal compounds SANT may be a promising candidate in anti-cancer drug discovery. It also provides novel strategies for using natural compounds to achieve optimized effect. Image 1 [ABSTRACT FROM AUTHOR]