Estrogens are considered the major breast cancer risk factor, and the carcinogenic potential of estrogens might be attributed to DNA modification caused by derivatives formed during metabolism. $17{\beta}$-estradiol ($E_2$), the main steroidal estrogen present in women, is metabolized via two major pathways: formation of 2-hydroxyestradiol (2-OH $E_2$) and 4-hydroxyestradiol ($4-OH\;E_2$) through the action of cytochrome P450 (CYP) 1A1 and 1B1, respectively. Previous reports suggested that $2-OH\;E_2$ has putative protective effects, while $4-OH\;E_2$ is genotoxic and has potent carcinogenic activity. Thus, the ratio of $2-OH\;E_2/4-OH\;E_2$ is a critical determinant of the toxicity of $E_2$ in mammary cells. In the present study, we investigated the effects of berberine on the expression profile of the estrogen metabolizing enzymes CYP1A1 and CYP1B1 in breast cancer MCF-7 cells. Berberine treatment produced significant induction of both forms at the level of mRNA expression, but with increased doses produced 16~ to 52~fold greater induction of CYP1A1 mRNA over CYP1B1 mRNA. Furthermore, berberine dramatically increased CYP1A1 protein levels but did not influence CYP1B1 protein levels in MCF-7 cells. In conclusion, we present the first report to show that berberine may provide protection against breast cancer by altering the ratio of CYP1A1/CYP1B1, could redirect $E_2$ metabolism in a more protective pathway in breast cancer MCF-7 cells.
Background: To evaluate efficacy and side effects of glycididazole sodium (CMNa) combined with chemotherapy (cisplatin plus 5-FU/folic acid, PLF) and radiotherapy in treating patients with locally advanced nasopharyngeal carcinoma. Materials and Methods: Patients with III~IV stage nasopharyngeal carcinoma (NPC),were randomly divided into treatment group (46 patients) and control group (45 patients). Both groups received radiotherapy concomitant with PLF chemotherapy. The treatment group at the same time cwas given CMNa ($800mg/m^2$ before radiotherapy), by l h intravenous drip, three times a week. Results: When the dose of radiation was over 60 Gy, complete response rates of nasopharyngeal tumor and lymph node metastases in treatment group were significantly higher than in the control group (93.5% vs 77.8%; 89.1% vs 93.5%, p<0.05). Three months after radiotherapy, complete response rate of nasopharynx cancer and lymph node metastases in treatment group was both 97.8%, again higher than in the control group (84.4% and 82.2%) (p<0.05). In the treatment group, 1, 3, 5 year disease-free survival rates were 95.7%, 86.7% and 54.5%; and in control group, the corresponding disease-free survival rates were 93.3%, 66.2% and 38.6%, respectively, the difference being statistically significant (log-rank =5.887, p=0.015). One, 3, 5 year overall survival rates in two groups of patients were 97.8%, 93.5%, 70.4% and 95.5%, 88.07%, 48.4%, respectively, again with a statistically significant difference (log-rank=6.470, p=0.011). Acute toxicity and long-term radiotherapy related toxicity in the two groups did not differ (p>0.05). Conclusions: Glycididazole sodium could improve curative effects without increasing adverse reactions when treating paitents with locally advanced nasopharyngeal carcinoma.
Dang, Yi-Wu;Zeng, Jing;He, Rong-Quan;Rong, Min-Hua;Luo, Dian-Zhong;Chen, Gang
Asian Pacific Journal of Cancer Prevention
/
v.15
no.12
/
pp.4969-4976
/
2014
Background: miR-152 is involved in the genesis and development of several malignancies. However, its role in HCC has not been fully clarified. The aim of this study was to investigate the clinicopathological significance of miR-152 and its effect on the malignant phenotype of HCC cells. Methods: miR-152 expression was detected using real-time quantitative RT-PCR in 89 pairs of HCC formalin-fixed paraffin-embedded and their adjacent tissues. Functionally, in vitro effects and mechanisms of action of miR-152 on proliferation, viability, caspase activity, apoptosis and motility were explored in HepG2, HepB3 and SNU449 cells, as assessed by spectrophotometry, fluorimetry, fluorescence microscopy, wound-healing and Western blotting, respectively. Results: miR-152 expression in HCC was downregulated remarkably compared to that in adjacent hepatic tissues. miR-152 levels in groups of advanced clinical stage, larger tumor size and positive HBV infection, were significantly lower than in other groups. A miR-152 mimic could suppress cell growth, inhibit cell motility and increase caspase activity and apoptosis in HCC cell lines. Furthermore, Western blotting showed that the miR-152 mimic downregulated Wnt-1, DNMT1, ERK1/2, AKT and TNFRS6B signaling. Intriguingly, inverse correlation of TNFRF6B and miR-152 expression was found in HCC and bioinformatics confirmed that TNFRF6B might be a target of miR-152. Conclusions: Underexpression of miR-152 plays a vital role in hepatocarcinogenesis and lack of miR-152 is related to the progression of HCC through deregulation of cell proliferation, motility and apoptosis. miR-152 may act as a tumor suppressor miRNA by also targeting TNFRSF6B and is therefore a potential candidate biomarker for HCC diagnosis, prognosis and molecular therapy.
Background: Patients with chronic liver diseases (CLD) may have compromised health related quality of life (HRQoL). Hepatitis B virus (HBV) infection has long been the leading cause of CLD including liver cancer and cirrhosis. Knowledge on different symptom profiles of CLD should help in development of comprehensive treatment and patient care plans. Objective: To access the facets of HRQoL in chronic liver diseases throughout their spectrum of severity. Materials and Methods: A cross-sectional study was conducted in the First Affiliated Hospital of Kunming Medical University in Yunnan Province of China. Both out- and inpatients undergoing treatment protocols for different HBV related liver disease states were consecutively collected from December 2012 to June 2013. ANOVA was used to compare the mean scores of EQ-5D and chronic liver disease questionnaire (CLDQ) among 5 disease groups. The relationship between demographic variables predicting global CLDQ scores and the domains of CLDQ was analysed. Results: A total of 1040 patients including 520 without complications, 91 with compensated cirrhosis, 198 with decompensated cirrhosis, 131 with HCC and 100 with liver failure were recruited. All domains of CLDQ, the means of EQ-5D value and EQ VAS exhibited significant decline with worsening of disease severity from uncomplicated HBV to liver failure. The multivariate regression demonstrated the reduction of mean scores of CLDQ domain at advanced stage. Patients with liver failure and HCC had more HRQoL impairment than other disease states. No effect of patient gender was found. Patient age was associated with 'fatigue' and 'worry' domains (p=0.006; p=0.004) but not with other domains and global scores of CLDQ and ED-5D. Conclusions: The HRQoL in chronic hepatitis B patients is greatly affected by disease states. Care for HBV-related diseases should consider not only the outcomes of treatment strategies but also improvement in patient wellbeing.
Aim: To examine lymph nodes obtained after lipolysis and liposuction of subcutaneous fat of the inguinal region of female vulvar cancer patients to explore the feasibility of clinical application. Methods: The field of operation was on the basis of the range of the conventional resection of inguinal lymph nodes. We injected lipolysis liquid fanwise, started liposuction after 15-20 minutes; then the subcutaneous fatty tissue was sucked out clearly by suction tube. We selected the first puncture holes located on 2-3 cm part below anterior superior spine, the others respectively being located 3cm and 6cm below the first for puncturing into the skin, imbedding a trocar to intorduce $CO_2$ gas and the specular body, and excise the lymph nodes by ultrasonic scalpel. The surgical field chamber was set with negative pressure drainage and was pressured with a soft saline bag after surgery. Results: A lacuna emerged from subcutaneous of the inguinal region after lipolysis and liposuction, with a wide fascia easily exposed at the bottom where lymph nodes could be readily excised. The number of lymph nodes of ten patients excised within the inguinal region on each side was 4-18. The excised average number of lymph nodes was 11 when we had mature technology. Conclusion: Most of adipose tissue was removed after lipolysis and liposuction of subcutaneous tissue of inguinal region, so that the included lymph nodes were exposed and easy to excise by endoscope. This surgery avoided the large incision of regular surgery of inguinal region, the results indicating that this approach is feasible and safe for used as an alternative technology.
Background: To study the effect of parecoxib, a novel cyclooxygenase-2 selective inhibitor, on the radiation response of colorectal cancer (CRC) cells and its underlying mechanisms. Materials and Methods: Both in vitro colony formation and apoptosis assays as well as in vivo mouse xenograft experiments were used to explore the radiosensitizing effects of parecoxib in human HCT116 and HT29 CRC cells. Results: Parecoxib sensitized CRC cells to radiation in vitro with a sensitivity enhancement ratio of 1.32 for HCT116 cells and 1.15 for HT29 cells at a surviving fraction of 0.37. This effect was partially attributable to enhanced apoptosis induction by parecoxib combined with radiation, as illustrated using an in vitro apoptosis assays. Parecoxib augmented the tumor response of HCT116 xenografts to radiation, achieving growth delay more than 20 days and an enhancement factor of 1.53. In accordance with the in vitro results, parecoxib combined with radiation resulted in less proliferation and more apoptosis in tumors than radiation alone. Radiation monotherapy decreased microvessel density (MVD) and microvessel intensity (MVI), but increased the hypoxia level in xenografts. Parecoxib did not affect MVD, but it increased MVI and attenuated hypoxia. Conclusions: Parecoxib can effectively enhance radiation sensitivity in CRC cells through direct effects on tumor cells and indirect effects on tumor vasculature.
Objectives: To explore the correlation between multi-slice spiral CT (MSCT) perfusion parameters and the expression of vascular endothelial growth factor (VEGF) as well as matrix metalloproteinase-2 (MMP-2) in breast cancer. Methods: Forty five breast cancer patients and 16 patients with benign breast tumor, both confirmed by pathology examination, were enrolled. All underwent MSCT perfusion imaging to obtain perfusion maps and data for parameters including blood flow (BF), blood volume (BV) and permeability surface (PS). Cancer patients did not receive treatment prior to surgery. The expression of VEGF and MMP-2 were examined with both immunohistochemistry and Western blotting. Results: The levels of VEGF and MMP-2 by immunohistochemistry were significantly higher in the breast cancer group (P < 0.01) than the benign tumor group. Relative OD values from Western blotting were also higher in cancer cases (P < 0.05). Similarly, the mean MSCT perfusion parameters (BF, BV, PS) were significantly higher in the breast cancer group (P < 0.01), BF and BV positively correlating with VEGF expression (r = 0.878 and 0.809 respectively, P < 0.01); PS and VEGF and MMP-2 expression were also positively correlated (r= 0.860, 0.786 respectively, P < 0.01). Conclusion: There is a correlation between breast cancer MSCT perfusion parameters and VEGF andMMP-2 expression, which might be useful for detection of breast lesions, qualitative diagnosis of breast cancer, and evaluation of breast cancer treatment.
Many epidemiological studies in Asian populations have investigated associations between the Arg399Gln gene polymorphism of X-ray repair cross complementing gene 1 (XRCC1) and risk of cervical carcinoma, but no conclusions have been available because of controversial results. Therefore a meta-analysis was conducted for clarification. Relevant studies were identified by searching the Pubmed, Embase, the Web of Science, Cochrane Collaboration's database, Chinese National Knowledge Infrastructure (CNKI), Wanfang database and China Biological Medicinse (CBM) until September, 2012. A total of eight studies were included in the present meta-analysis, which described 1,759 cervical carcinoma cases and 2,497 controls. Odds ratios (ORs) and corresponding 95% confidence intervals (95%CIs) as effect size were calculated by fixed-effect or random-effect models. The overall results indicated that the XRCC1-399G/A polymorphism was marginally associated with cervical carcinoma in Asians: OR (95%CI): 1.16 (1.07, 1.26) in the G/A vs G/G inheritance model, 1.24 (0.87, 1.76)in A/A vs G/G inheritance model, 1.13 (1.01, 1.27) in the dominant inheritance model and 1.18 (0.94, 1.47) in the recessive inheritance model. Subgroup analyses on sample size showed no significant correlation in the small-sample size group but the large-sample size group was consistent with the outcomes of overall meta-analysis. In the subgroup analysis by regions, we only found significant association under the G/A vs G/G inheritance model in the Chinese population. For the non-Chinese populations, no correlation was detected in any genetic inheritance model. In the Asian populations, XRCC1-399G/A gene polymorphism was implied to be associated with cervical carcinoma.
Background: Potential disadvantages of blood transfusion during curative gastrectomy for gastric cancer have been reported, and the role of peri-operative transfusions remains to be ascertained. Thus, the aim of our study was to survey its impact in patients with gastric cancer undergoinging gastrectomy. Materials and Methods: Clinical data of patients receiving curative gastrectomy at Far Eastern Memorial Hospital were obtained. Findings for pre-operative anemia states, pre-, peri- and post-operative transfusion of red blood cell (RBC) products as well as post-operative complication events were collected for univariate analysis. Results: A total of 116 patients with gastric cancer received gastrectomy at Far Eastern Memorial Hospital from 2011 to 2014. Both pre-operative and intra- and post-operative transfusion of RBC products were markedly associated with post-operative infectious events (OR: 3.70, 95% CI: 1.43-9.58, P=0.002; OR: 8.20, 95% CI: 3.11-22.62, P<0.001, respectively). In addition, peri- and post-operative RBC transfusion was significantly associated with prolonged hospital stay from admission to discharge (OR: 8.66, 95% CI: 1.73-83.00, P=0.002) and post-operative acute renal failure (OR: 19.69, 95% CI: 2.66-854.56, P<0.001). Also, the overall survival was seemingly decreased by peri-operative RBC transfusion in our gastric cancer cases (P=0.078). Conclusions: Our survey indicated that peri-operative RBC transfusion could increase the risk of infectious events and acute renal failure post curative gastrectomy as well as worsen the overall survival in gastric cancer cases. Hence, unnecessary blood transfusion before, during and after curative gastrectomy should be avoided in patients with gastric cancer.
Background: The effect and possible mechanism of traditional Chinese medicine, baicalin, on the PI3K/Akt signaling pathway in drug-resistant human myeloid leukemia HL-60/ADR cells have been investigated in this current study. Methods: HL-60/ADR cells were treated by 20, 40, $80\;{\mu}mol/L$ baicalin followed by cell cycle analysis at 24h. The mRNA expression level of the apoptosis related gene, Bcl-2 and bad, were measured by RT-PCR on cells treated with $80\;{\mu}mol/L$ baicalin at 12, 24 and 48hr. Western blot was performed to detect the changes in the expression of the proteins related to HL-60/ADR cell apoptosis and the signaling pathway before and after baicalin treatment, including Bcl-2, PARP, Bad, Caspase 3, Akt, p-Akt, NF-${\kappa}B$, p-NF-${\kappa}B$, mTOR and p-mTOR. Results: Sub-G1 peak of HL-60/ADR cells appeared 24 h after $20\;{\mu}mol/L$ baicalin treatment, and the ratio increased as baicalin concentration increased. Cell cycle analysis showed 44.9% G0/G1 phase cells 24 h after baicalin treatment compared to 39.6% in the control group. Cells treated with $80\;{\mu}mol/L$ baicalin displayed a trend in decreasing of Bcl-2 mRNA expression over time. Expression level of the Bcl-2 and PARP proteins decreased significantly while that of the PARP, Caspase-3, and Bad proteins gradually increased. No significant difference in Akt expression was observed between treated and the control groups. However, the expression levels of p-Akt, NF-${\kappa}B$, p-NF-${\kappa}B$, mTOR and p-mTOR decreased significantly in a time-dependent manner. Conclusions: We conclude that baicalin may induce HL-60/ADR cell apoptosis through the PI3K/AKT signaling pathway.
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