Orobanone analogues from acid-promoted aromatization rearrangement of curcumol inhibit hypoxia-inducible factor-1 (HIF-1) in cell-based reporter assays.

In this paper, the mechanism of orobanone analogues formation via aromatization rearrangement of curcumol was minutely explored. Aromatization of curcumol with acetone under acidic condition was selected as the model reaction. The formation of a stable aromatic system was the driving force for this reaction. Based on the model reaction, other four new orobanone analogues were prepared through curcumol reacting with different carbonyl compounds. The results showed that the stability of carbocation, which was generated from the carbonyl compounds, and the steric hindrance were main factors affecting the aromatization. We also synthesized the analogue of aromaticane B using compound 2. In vitro anti-proliferative activity of some derivatives were tested by MTT assay. Two derivatives showed weak anti-tumor effect on two cancer cell lines (HepG2 and MCF7) under normoxia. Four orobanone analogue 2, 5, 6 and 9 significantly inhibited hypoxia-induced HIF-1 luciferase reporter activity in HeLa cells with the IC50 values of 13.6, 6.6, 2.4 and 18.2 µM, respectively.

The association of semaphorin 5A with lymph node metastasis and adverse prognosis in cervical cancer.

BACKGROUND: Semaphorin 5A has been linked to tumor growth, invasion, and metastasis in pancreatic cancer. However, the role of semaphorin 5A in cervical cancer is not known. Our aim is to investigate the prognostic value of semaphorin 5A and its potential role in lymphangiogenesis and invasion in cervical cancer. METHODS: In this study, pathological features and clinical data of 232 cervical cancer patients were retrospectively reviewed. Semaphorin 5A protein and mRNA expression was detected by immunohistochemistry and quantitative real-time reverse transcription-polymerase chain reaction, respectively. In vitro, we determined the role and mechanistic pathways of semaphorin 5A in tumor progression in cervical carcinoma cell lines. RESULTS: Semaphorin 5A expression was significantly higher in stage IIb tumors than in stage Ia, Ib, and IIa tumors. High semaphorin 5A expression was significantly associated with pelvic lymph node metastasis, lymphovascular permeation, and poor survival. Semaphorin 5A induced lymphangiogenesis through a plexin-B/Met/vascular endothelial growth factor-C pathway. Semaphorin 5A also increased cervical cancer cell invasion by stimulating the expression and activity of matrix metalloproteinase-2 and matrix metalloproteinase-9 via PI3K/AKT and plexin-B3. CONCLUSION: Our findings indicate that semaphorin 5A may represent a poor prognostic biomarker and anti-metastasis therapeutic target in cervical cancer.

Wrist-ankle acupuncture and ginger moxibustion for preventing gastrointestinal reactions to chemotherapy: A randomized controlled trial.

OBJECTIVE: To evaluate the effects of wrist-ankle acupuncture combined with ginger moxibustion against gastrointestinal tract reactions (nausea, vomiting, and constipation) to chemotherapy in cancer patients. METHODS: A total of 60 patients with gynecological tumors treated by chemotherapy were randomly divided into two groups. The treatment group (30 cases) underwent wrist-ankle acupuncture and ginger moxibustion, whereas tropisetron hydrochloride and dexamethasone were intravenously administered to the control group (30 cases) during chemotherapy. RESULTS: The frequency of nausea in the treatment group was significantly less than that of the control group from the 2nd to the 5th day of chemotherapy (P<0.01). The anti-emetic effect in the treatment group was significantly better than that in the control group on the 3rd day of therapy (P<0.05). The incidence rate of constipation was significantly lower in the treatment group than that in the control group (P<0.01). Furthermore, the cost of therapy for the treatment group was significantly lower than that of the control group (P<0.01). Only 1 patient manifested a post-acupuncture side effect in the form of subcutaneous blood stasis. CONCLUSION: Wrist-ankle acupuncture combined with ginger moxibustion could prevent gastrointestinal tract reactions to chemotherapy in cancer patients. In addition, the proposed method had fewer side effects, lower cost, and less risk.

Wrist-ankle acupuncture for pain after transcatheter arterial chemoembolization in patients with liver cancer: a randomized controlled trial.

This study was designed to evaluate the analgesic effect of wrist-ankle acupuncture (WAA) for patients with primary liver cancer (PLC) after transcatheter arterial chemoembolization (TACE). Sixty PLC patients with post-TACE visual analog pain intensity scores greater than 3 were divided equally into two groups receiving either WAA or oral morphine sulphate (MOR) for post-TACE pain. Pain intensity scores were reassessed at 1, 2, 4, and 6 h after analgesic intervention. Patients were also monitored for adverse reactions to analgesic treatment. Pain scores recorded when the patients first felt pain after TACE showed no statistical difference between the two groups (p > 0.05). WAA and MOR had indistinguishable degrees of pain relief 1, 2, and 4 h after analgesic intervention (p > 0.05). At 6 h after intervention, the WAA group experienced significantly greater pain relief than the MOR group (p < 0.05). Incidence of abdominal distension was lower in the WAA group than in the MOR group (p < 0.05). The results suggest that WAA not only had an analgesic effect equal to or greater than MOR in PLC patients with moderate to severe post-TACE pain, but also reduced the incidence of post-operative abdominal distention.

[Effects of Chinese herbal medicine Neiyi Recipe-medicated serum on angiopoiesis of endometriosis in the chick chorioallantoic membrane model].

OBJECTIVE: To compare angiopoiesis ability of eutopic and ectopic endometrial tissue isolated from women with endometriosis and endometrium isolated from women without endometriosis (control), and to explore the inhibitory effects of medicated serum of Neiyi Recipe, a compound traditional Chinese herbal medicine. METHODS: Chick chorioallantoic membrane (CAM) model of endometriosis was established by transplanting endometrium onto CAM. The CAMs were then hatched with blank serum or medicated serum of danazol or Neiyi Recipe, which were prepared in rats by orally administering. The sizes of the transplanted tissue and new vessels around the transplanted tissue were measured. Expression of vascular endothelial growth factor (VEGF) was detected by immunohistochemical method. RESULTS: There was no difference in the sizes of transplanted tissue among CAM models of ectopic and eutopic endometrial tissue isolated from women with endometriosis or control (P>0.05), and more new vessels were found around the ectopic and eutopic endometrial tissue than the endometrial tissue of control (P<0.05). Compared with the controls, the size of the transplanted tissue and positive area of new vessels were significantly inhibited by Neiyi Recipe-medicated serum (P<0.01, P<0.05), and similar changes happened in the danazol groups, except for the size of transplanted tissue from ectopic endometrial tissue (P>0.05). Expression of VEGF was significantly higher in eutopic and ectopic endometrial tissue than in the control (P<0.01); the level of VEGF obviously reduced in the Neiyi Recipe and danazol groups (P<0.01), but no significant difference was detected between them. CONCLUSION: Endometrium from women with endometriosis stimulates the formation of new vessels by increase the expression of VEGF. Neiyi Recipe-medicated serum significantly decreases the expression of VEGF in eutopic and ectopic endometrial tissues and thus restrains the formation of new vessels, reduces the blood supply and inhibits growth of ectopic endometrial tissue, which are similar to danazol, but has greater efficacy in suppressing the expression of VEGF.

Health-related quality of life evaluated by tumor node metastasis staging system in patients with hepatocellular carcinoma.

AIM: To investigate and evaluate the change in health-related quality of life (HRQoL) by tumor node metastasis (TNM) staging system in patients with hepatocellular carcinoma (HCC). METHODS: A total of 140 patients diagnosed with HCC between June 2008 and April 2009 in our department were enrolled to this study. One hundred and thirty-five (96.5%) patients had liver cirrhosis secondary to hepatitis B virus (HBV) infection, 73 (54.07%) of them being HBV DNA positive; the other etiologies of liver cirrhosis were alcoholic liver disease (1.4%), hepatitis C (1.4%) or cryptogenic (0.7%). All subjects were fully aware of their diagnosis and provided informed consent. HRQoL was assessed before treatment using the functional assessment of cancer therapy-hepatobiliary (FACT-Hep) questionnaire. Descriptive statistics were used to evaluate demographics and disease-specific characteristics of the patients. One-way analysis of variance and independent samples t tests were used to compare the overall FACT-Hep scores and clinically distinct TNM stages. Scores for all FACT-Hep items were analyzed by frequency analyses. The mean scores obtained from the FACT-Hep in different Child-Pugh classes were also evaluated. RESULTS: The mean FACT-Hep scores were reduced significantly from TNM Stage I to Stage II, Stage IIIA, Stage IIIB group (687 ± 39.69 vs 547 ± 42.57 vs 387 ± 51.24 vs 177 ± 71.44, P = 0.001). Regarding the physical and emotional well-being subscales, scores decreased gradually from Stage I to Stage IIIB (P = 0.002 vs Stage I; P = 0.032 vs Stage II; P = 0.033 vs Stage IIIA). Mean FACT-Hep scores varied by Child-Pugh class, especially in the subscales of physical well-being, functional well-being and the hepatobiliary cancer (P = 0.001 vs Stage I; P = 0.036 vs Stage II; P = 0.032 vs Stage IIIA). For the social and family well-being subscale, only Stage IIIB scores were significantly lower as compared with Stage I scores (P = 0.035). For the subscales of functional well-being and hepatobiliary cancer, there were significant differences for Stages IIΙ, IIIA and IIIB (P = 0.002 vs Stage I). CONCLUSION: HRQoL of patients with HCC worsens gradually with progression of TNM stages. The most impaired subscales of HRQoL, as measured by FACT-Hep, were physical and emotional well-being.