Huayu Pill () Promotes Fluorescent Doxorubicin Delivery to Tumors in Mouse Model of Lung Cancer.

OBJECTIVE: To study the effect and mechanism of Huayu Wan (, HYW) in combination of chemotherapy of tumor treatment. METHODS: HYW serum was added in Lewis cells to assess its impact on fluorescent doxorubicin delivery in vitro. Then, Lewis tumor cells was implanted in C57BL/6 mice via xenograft transplantation. Tumor growth was measured and signal intensity corresponding to blood flow was assessed by laser doppler perfusion imaging (LDPI). Finally, the effect of HYW on the effificacy of doxorubicin was studied. RESULTS: HYW can improve the transfer of fluorescent doxorubicin into cells. The blood flow signal in the tumor tissues of the HYW group was higher than that of the control group (P<0.01). Furthermore, HYW improved drug delivery of doxorubicin to tumor tissues, and this activity was associated with HYW-induced microvascular proliferation (P<0.01). CONCLUSIONS: HYW can promote microangiogenesis and increase blood supply in tumor tissues, which in turn may increase the risk of metastasis. At the same time, HYW increases drug delivery and improves the effificacy of chemotherapy drugs through vascular proliferation. Therefore, rational judgment must be exercised when considering applying HYW to an antitumor regimen.

Efficacy of acupuncture in the prevention and treatment of chemotherapy-induced nausea and vomiting in patients with advanced cancer: a multi-center, single-blind, randomized, sham-controlled clinical research.

BACKGROUND: Chemotherapy-induced nausea and vomiting (CINV) is a common and distressing side effect. We conducted this clinical trial to compare the effectiveness of true acupuncture vs. sham acupuncture in controlling chemotherapy-induced nausea and vomiting (CINV) among patients with advanced cancer. METHODS: A total of 134 participants were randomly allocated into true acupuncture (TA) (n = 68) and sham acupuncture (SA) (n = 66) groups. Participants in both groups received acupuncture session twice on the first day of chemotherapy, and once consecutively on the following 4 days. The primary outcome was using the Common Terminology Criteria for Adverse Events (CTCAE) to assess CINV. The secondary outcome measures were the Eastern Cooperative Oncology Group score (ECOG), Simplified Nutritional Appetite Questionnaire (SNAQ), and Hospital Anxiety and Depression scale (HADS). RESULTS: Compared to the SA group, the TA group didn't show significant improvement in complete response rates of chemotherapy-induced nausea and vomiting (all P > 0.05). However, the TA group could modestly reduce the severity of nausea (from day-3 to day-21, P < 0.05) or vomiting (from day-4 to day-21, P < 0.05), which is notably superior to the control group. Besides, TA promoted the nutritional status of patients with a significantly higher score comparing to the SA group on day 14 (21.82 vs.20.12, P = 0.003) and day 21 (22.39 vs. 20.43, P = 0.001). No apparent differences were found in anxiety and depression assessment between these groups. Participants in both groups were well tolerant of acupuncture therapy. There was no adverse event occurs in our study. CONCLUSION: Acupuncture as an adjunctive approach could alleviate the severity of chemotherapy-induced nausea and vomiting compared to the sham control, even though the effect of acupuncture in preventing CINV occurring is relatively modest.

Chinese Medicine Yishen Jiangu Granules () on Aromatase Inhibitor-Associated Musculoskeletal Symptoms.

OBJECTIVE: To assess the effectiveness of Yishen Jiangu Granules (, YSJGG) on aromatase inhibitor-associated musculoskeletal symptoms (AIMSS). METHODS: A single-arm, open-label study was conducted in 34 postmenopausal women with breast cancer who experienced AIMSS. Patients were treated with YSJGG for 12 weeks (12.4 g orally twice daily). The primary outcome was a change in the mean worst pain score of Brief Pain Inventory-Short Form (BPI-SF) over 12 weeks, and the second outcomes included changes in pain severity and pain-related interference of BPI-SF and Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), Modified Score for the Assessment of Chronic Rheumatoid Affections of the Hands (M-SACRAH), the Functional Assessment of Cancer Therapy-Breast (FACT-B), bone mineral density (BMD) and blood indices such as calcium (Ca), phosphate (P), and alkaline phosphatase (ALP). RESULTS: Of 37 women recruited, 30 initiated the therapy and 24 were evaluable at 12 weeks. The primary outcome (BPI-SF worst pain scores) achieved a 2.17-point reduction compared with baseline (5.75±1.87 vs 3.58±2.15, P<0.01). There were reductions in pain severity (decreased 1.65, P<0.01) and pain-related interference (decreased 2.55, P<0.01). The changes in WOMAC and M-SACRAH scores were similar to BPI-SF (P<0.05). In the FACT-B, only physical well-being and functional well-being were improved compared with baseline (P<0.05). No clinical differences were found in BMD, Ca, P and ALP. CONCLUSION: YSJGG is an effective and well-tolerated agent to reduce AIMSS.

Gubenyiliu II Inhibits Breast Tumor Growth and Metastasis Associated with Decreased Heparanase Expression and Phosphorylation of ERK and AKT Pathways.

Gubenyiliu II (GYII), a Traditional Chinese Medicine (TCM) formula used in our hospital, has shown beneficial effects in cancer patients. In this study, we investigated the molecular mechanisms underlying the beneficial effects of GYII on murine breast cancer models. GYII showed significant inhibitory effects on tumor growth and metastasis in the murine breast cancer model. Additionally, GYII suppressed the proliferation of 4T1 and MCF-7 cells in a dose-dependent manner. A better inhibitory effect on 4T1 cell proliferation and migration was found in the decomposed recipes (DR) of GYII. Moreover, heparanase expression and the degree of angiogenesis were reduced in tumor tissues. Western blot analysis showed decreased expression of heparanase and growth factors in the cells treated with GYII and its decomposed recipes (DR2 and DR3), and thereby a reduction in the phosphorylation of extracellular signal-regulated kinase (ERK) and serine-threonine kinase (AKT). These results suggest that GYII exerts anti-tumor growth and anti-metastatic effects in the murine breast cancer model. The anti-tumor activity of GYII and its decomposed recipes is, at least partly, associated with decreased heparanase and growth factor expression, which subsequently suppressed the activation of the ERK and AKT pathways.

Effect of acupuncture in prevention and treatment of chemotherapy-induced nausea and vomiting in patients with advanced cancer: study protocol for a randomized controlled trial.

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.

Chinese Herbal Medicine as Adjunctive Therapy to Chemotherapy for Breast Cancer: A Systematic Review and Meta-Analysis.

Chinese herbal medicine (CHM) has been increasingly employed during therapy for breast cancer, but its efficacy remains a matter of debate. This systematic review examined randomized controlled trials to provide a critical evaluation of this treatment. The results demonstrated that the combined use of CHM with chemotherapy may improve the immediate tumor response and reduce chemotherapy-associated adverse events. Our findings highlight the poor quality of Chinese studies, and additional well-designed randomized controlled trials addressing the role of CHM are warranted. The lack of molecular-based evidence for CHM and Zheng has resulted in a limited understanding and acceptance of CHM and traditional Chinese medicine in Western countries. We believe that researchers should immediately explore a CHM-based cure, and CHM should be applied to routine care as soon as conclusive data are available.

Spatholobus suberectus Column Extract Inhibits Estrogen Receptor Positive Breast Cancer via Suppressing ER MAPK PI3K/AKT Pathway.

Although Chinese herbal compounds have long been alternatively applied for cancer treatment in China, their treatment effects have not been sufficiently investigated. The Chinese herb Spatholobus suberectus is commonly prescribed to cancer patients. HPLC analysis has shown that the main components of Spatholobus suberectus are flavonoids that can be classified as phytoestrogens, having a structure similar to estrogen. This study was designed to investigate the effects of Spatholobus suberectus column extract (SSCE) on the estrogen receptor-positive (ER+) breast cancer cell line MCF-7 and its possible molecular mechanism. In our study, MTT assay was performed to evaluate cell viability. The results show that SSCE (80, 160, and 320 µg/ml) significantly decreased the viability of MCF-7 cells. SSCE also triggered apoptosis, arrested the cell cycle at the G0/G1 phase, and inhibited cell migration. A dual-luciferase reporter system showed that SSCE suppressed intranuclear p-ER activity; Western blot analysis confirmed the repressed expression of phosphorylated-ER alpha (p-ERα), ERK1/2, p-ERK1/2, AKT, p-AKT, p-mTOR, PI3K, and p-PI3K, indicating that SSCE suppressed the MAPK PI3K/AKT signaling pathway. Collectively, our results suggest that SSCE causes apoptosis, an arrest in the G0/G1 phase, and a decrease in migration in ER+ MCF-7 cells via hypoactivity of the ER and suppression of the MAPK PI3K/AKT pathway.

Heijiangdan ointment relieves oxidative stress from radiation dermatitis induced by (60)Co γ-ray in mice.

OBJECTIVE: To investigate the effects of Heijiangdan Ointment ( HJD) on oxidative stress in (60)Co γ-ray radiation-induced dermatitis in mice. METHODS: Female Wistar mice with grade 4 radiation dermatitis induced by (60)Co γ-rays were randomly divided into four groups (n=12 per group); the HJD-treated, recombinant human epidermal growth factor (rhEGF)-treated, Trolox-treated, and untreated groups, along with a negative control group. On the 11th and 21st days after treatment, 6 mice in each group were chosen for evaluation. The levels of superoxide dismutase (SOD), malondialdehyde (MDA), and lactate dehydrogenase (LDH) were detected using spectrophotometric methods. The fibroblast mitochondria were observed by transmission electron microscopy (TEM). The expressions of fibroblast growth factor 2 (FGF-2) and transforming growth factor ß1 (TGF-ß1) were analyzed by western blot. RESULTS: Compared with the untreated group, the levels of SOD, MDA and LDH, on the 11th and 21st days after treatment showed significant difference (P<0.05). TEM analysis indicated that fibroblast mitochondria in the untreated group exhibited swelling and the cristae appeared fractured, while in the HJD group, the swelling of mitochondria was limited and the rough endoplasmic reticulum appeared more relaxed. The expressions of FGF-2 and TGF-ß1 increased in the untreated group compared with the negative control group (P<0.05). After treatment, the expression of FGF-2, rhEGF and Trolox in the HJD group were significantly increased compared with the untreated group (P<0.05), or compared with the negative control group (P<0.05). The expression of TGF-ß1 showed significant difference between untreated and negative control groups (P<0.05). HJD and Trolox increased the level of TGF-ß1 and the difference was marked as compared with the untreated and negative control groups (P<0.05). CONCLUSION: HJD relieves oxidative stress-induced injury, increases the antioxidant activity, mitigates the fibroblast mitochondrial damage, up-regulates the expression of growth factor, and promotes mitochondrial repair in mice.

Inhibitory effects of Guben Yiliu Formula II (II) and its blood activation prescriptions on the growth of MCF-7 human breast cancer xenografts in nude mice.

OBJECTIVE: To investigate the inhibitory effects of Guben Yiliu Formula II(II, GFII) and its blood activation prescription (BAP) on the growth of MCF-7 human breast cancer xenografts in nude mice, and explore their mechanisms of action. METHODS: After the establishment of the MCF-7 human breast cancer xenograft model in nude mice, the mice in the GFII and BAP groups were administered with GFII (6.56 g/mL) and BAP (1.65 g/mL) by gavage for 28 days, respectively. The tumor volume and weight were measured twice a week throughout the treatment period. Apoptotic cells were identified by terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling. The expression of microtubule associated protein 1 light chain 3 (LC3) was examined by immunohistochemistry, and Western blotting analysis was performed to detect the expression of anti-apoptotic protein Bcl-2 and LC3, as well as the effects on phosphatidylinositol-3-kinase/protein kinase B/mammalian target of rapamycin (PI3K/Akt/mTOR) signaling pathway. RESULTS: Compared with the control group, the GFII and BAP groups could significantly inhibit the growth of MCF-7 human breast cancer xenografts in nude mice. The expression of Bcl-2 protein was lower in the GFII and BAP than in the control group, whereas both the percentage of apoptotic cells and LC3-II/LC3-I ratio were higher than in the control group. In addition, significantly reduced expression of phospho-Akt, phosphor-mTOR and mTOR were observed in the blood activation group (P<0.05). CONCLUSIONS: To some extent, the GFII and its BAP can exert their inhibitory effect on the growth of MCF-7 human breast cancer xenografts by inducing the cell apoptosis and autophagy. In addition to the induction of cell apoptosis, we also found that the BAP of GFII could induce cell autophagy by inhibiting of PI3K/Akt/mTOR signaling pathway, and then suppress the breast cancer cell growth.

Effects of the traditional Chinese medicine Yi Shen Jian Gu granules on aromatase inhibitor-associated musculoskeletal symptoms: a study protocol for a multicenter, randomized, controlled clinical trial.

BACKGROUND: Aromatase inhibitors (AIs) are widely used as an adjuvant endocrine treatment in postmenopausal women with early-stage breast cancer. One of the main adverse effects of AIs is musculoskeletal symptoms, which leads to a lower quality of life and poor adherence to AI treatment. To date, no effective management of aromatase inhibitor-associated musculoskeletal symptoms (AIMSS) has been developed. METHODS/DESIGN: To determine whether the traditional Chinese medicine Yi Shen Jian Gu granules could effectively manage AIMSS we will conduct a multicenter, randomized, double-blind, placebo-controlled clinical trial. Patients experiencing musculoskeletal symptoms after taking AIs will be enrolled and treated with traditional Chinese medicine or placebo for 12 weeks. The primary outcome measures include Brief Pain Inventory-Short Form, Western Ontario and McMaster Universities Osteoarthritis Index, and Modified Score for the Assessment and Quantification of Chronic Rheumatoid Affections of the Hands, which will be obtained at baseline and at 4, 8, 12 and 24 weeks. DISCUSSION: The results of this study will provide a new strategy to help relieve AIMSS. TRIAL REGISTRATION ISCTN: ISRCTN06129599 (assigned 14 August 2013).

[Comparative study on the methods of Chinese medicine and Western medicine therapeutic evaluation for advanced non-small cell lung cancer].

OBJECTIVE: To compare the differences and characteristics in Chinese medicine (CM) and Western medicine therapeutic evaluation methods in the application of advanced non-small cell lung cancer. METHODS: A total of 200 cases of advanced non-small cell lung cancer from 3 subcenters were enrolled the study and assigned to two groups, 104 in the CM group treated with CM injection combined with treatment based on syndrome differentiation, 96 in the chemotherapy group treated with the international chemothearapy scheme, both the course of treatment was 6 weeks. Their short-term therapeutic effects were observed by the "clinic efficacy appraisal standard of therapy for advanced lung cancer with CM" simultaneously and by the follow-up Western medical solid tumor's effect evaluation criterion, including clinical symptoms, tumor body, Karnorfsky score, body weight and immune function evaluation. RESULTS: According to WHO solid tumor's effect evaluation criterion, the efficacy of the chemotherapy group was much better than that of the CM group (P < 0.01). While, according to the "clinic efficacy appraisal standard of therapy for advanced lung cancer with CM", the efficacy of the CM group was better than that of the chemotherapy group without statistical difference (P = 0.05), however, there was a very strong trend of appearing difference. There was difference inult o the results of the two evaluation methods. CONCLUSION: Compared with WHO solid tumor's effect evaluation criterion, "the clinic efficacy appraisal standard of therapy for advanced lung cancer with CM" can reflect more features and advantages of CM for cancer treatment, having value for further study.

[Effects of Lignum Sappen on growth and metastases of Lewis lung carcinoma at different phases in C57BL/6 mice].

OBJECTIVE: To observe the effects of Lignum Sappan (LS) on the growth and metastases of transplanted Lewis lung carcinoma (LLC) in mice and investigate its partial mechanism of action. METHODS: C57BL/6 mice were established in LLC model and divided into six groups in random: Group A was untreated; Group B was treated by chemotherapy (CM) only; Groups C-F were treated respectively with low-dose LS, high-dose LS, CM + low-dose LS and CM + high-dose LS, via intragastric administration for 21 successive days. Mice were sacrificed in batches at different time points (d 7, d 14 and d 21) to observe the tumor inhibition rate and the metastases suppressing rate was measured dynamically. Meantime, the CD44 expression in tumor cells was measured by flow cytometry and serum P-selectin concentration was measured by ELISA assay. RESULTS: Tumor weight in all treated groups, except Group C, was lower than that in Group A at the three time points (P < 0.05, P < 0.01), and that was lower in Group F than in Group B at the corresponding time points (P < 0.05, P < 0.01). Comparisons of CD44+ in tumor cells showed that as compared with Group A, on d 7, it was lower in Groups B and D (P < 0.01); on d 14, it was lower in Group E (P < 0.01) and Group F (P < 0.05); and on d 21, it was lower in Groups E and F (P < 0.01). As for the concentration of P-selectin, the intergroup comparisons showed that it was lower in Groups B-F on d 7 and in Group F on d 21 than that in Group A (P < 0.05 or P < 0.01), but showed insignificant difference in comparing the Group A with all the treated Groups on d 14 (P > 0.05). CONCLUSION: LS and CM +LS could inhibit the growth and metastases of LLC, and shows inhibition on CD44 expression in tumor cells and P-selectin level in serum, which may be one of the mechanisms of LS in suppressing tumor metastasis.