Background: A dense breast not only reduces the sensitivity of mammography but also is a moderate independent risk factor for breast cancer. The percentage of Western women with fat breast tissue is higher aged 40 years or older. To a certain extent, mammography as a first choice of screening imaging method for Western women of this group is reasonable. Hitherto, the frequency and age distribution of mammographic breast density patterns among Chinese women had not been characterized. The purpose of this study was to investigate the frequency and age distribution of mammographic breast density patterns among a group of Chinese screening women and breast cancer patients in order to provide useful information for age-specific guidelines for breast cancer screening in Chinese women. Methods: A retrospective review of a total of 3,394 screening women between August and December 2009 and 2,527 breast cancer patients between July 2011 and June 2012 was conducted. Descriptive analyses were used to examine the association between age and breast density. The significance of differences of breast density between the screening women and the breast cancer patients was examined using nonparametric tests. Results: There was a significant inverse relationship between age and breast density overall (r=-0.37, p< 0.01). Breast density of the breast cancer patients in the subgroups of 40-49 years old was greater compared with that of the screening women, the same in those aged 50-54 years and in those 55 years old or older, less than in the screening group. Conclusions: With regard to the Chinese women younger than 55 years old, the diagnostic efficiency of breast cancer screening imaging examinations may be potentially improved by combining screening mammography with ultrasound.
Context: Interest exits in whether TNF-alpha antagonists increase the risk of breast cancer and total malignancies in patients with rheumatoid arthritis (RA). Objectives: To analyze the risk of malignancies, especially breast cancer, in patients with RA enrolled in randomized control trials (RCTs). Methods: A systematic literature search for RCTs from 1 January 1998 to 1 July 2013 from online databases, such as PubMed, WILEY, EMBASE, ISI web of knowledge and Cochrane Library was conducted. Studies included RCTs that compared the safety of at least one dose of the five TNF-${\alpha}$ antagonists with placebo or methotrexate (MTX) (or TNF-${\alpha}$ antagonists plus MTX vs placebo plus MTX) in RA patients for more than 24 weeks and imported all the references into document management software EndNote${\times}6$. Two independent reviewers selected studies and extracted the data about study design, patients' characteristics and the type, number of all malignancies. Results: 28 RCTs from 34 records with 11,741 patients were analyzed. Of the total, 97 developed at least one malignancy during the double-blind trials, and breast cancer was observed in 17 patients (17.5% of total malignancies). However, there was no statistically significant increased risk observed in either the per protocol (PP) model (OR 0.65, 95%CI [0.22, 1.93]) or the modified intention to treat (mITT) model (OR 0.75, 95%CI [0.25, 2.21]). There were also no significant trend for increased risk of total malignancies on anti-TNF-${\alpha}$ therapy administered at approved doses in either model (OR, 1.06, 95%CI [0.64, 1.75], and OR, 1.30, 95%CI [0.80, 2.14], respectively). As to the two models, modified intention to treat model analysis led to higher estimation than per protocol model analysis. Conclusions: This study did not find a significantly increased risk of breast cancer and total malignancies in adults RA patients treated with TNF-${\alpha}$ antagonists at approved doses. However, it cannot be ignored that more patients developed malignancies with TNF-${\alpha}$ antagonists therapy compared with patients with placebo or MTX, in spite of the lack of statistical significance, so that more strict clinical trials and long-term follow-up are needed, and both mITT and PP analyses should be used in such safety analyses.
Introduction: Some non-small cell lung cancer (NSCLC) tumor cells are insensitive to tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) -based therapy. This study was conducted to examine the effect of embelin on the sensitivity of the A549 NSCLC cell line to TRAIL receptor2 (TRAILR2) monoclonal antibodies and to investigate the potential mechanisms. Materials and Methods: A549 cells were treated with embelin, TRAILR2 mAb or a combination of both. Cell viability was measured using ATPlite assay and apoptosis rates were determined by flow cytometry with AnnexinV-FITC and propidium iodide staining, with the expression levels of proteins analyzed by Western blotting. Results: The cell survival rate of separate treatments with 100 ng/ml TRAILR2 antibody or 25 uM embelin were $81.5{\pm}1.57%$ and $61.7{\pm}2.84%$, respectively. Their combined use markedly decreased cell viability in A549 cells to $28.1{\pm}1.97%$ (P<0.05). The general caspase inhibitor Z-VAD-FMK could inhibit the embelin-enhanced sensitivity of A549 cells to TRAILR2 mAb ($75.97{\pm}3.17%$)(P<0.05). Both flow cytometry and cell morphological analysis showed that embelin was able to increase TRAIL-induced apoptosis in A549 cells. Combined treatment with embelin and TRAILR2 mAb augmented the activation of initiator caspases and effector caspase. In addition, A549 cells showed increasing levels of TRAILR2 protein and decreasing levels of Bcl-2, survivin and c-FLIP following the treatment with embelin+TRAILR2 mAb. Conclusions: Embelin could enhance TRAIL-induced apoptosis in A549 cells. The synergistic effect of the combination treatment might be due to modulation of multiple components in the TRAIL receptor-mediated apoptotic signaling pathway, including TRAILR2, XIAP, survivin, Bcl-2 and c-FLIP.
Wang, Shi-Ying;Zhu, Wen-Hao;Vargulick, Sonya;Lin, Sam Bill;Meng, Zhi-Qiang
Asian Pacific Journal of Cancer Prevention
/
제14권10호
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pp.5995-6000
/
2013
Background: Nausea and vomiting after transcatheter arterial chemoembolization (TACE) for hepatocellular carcinoma (HCC) are common in clinical practice, but few studies have reported the incidence and risk factors of such events. Objective: The purpose of this study was to analyze the incidence and risk factors of nausea and vomiting after TACE for HCC. Methods: This study was a single-center retrospective analysis of a prospectively maintained database. Between May 2010 and October 2012, 150 patients with HCC were analyzed for incidence and preprocedural risk factors. Results: The incidence of postembolization nausea and vomiting was 38.8% and 20.9%, respectively, in patients with HCC. Patients who developed nausea had lower levels (<100 IU/L) of serum alkaline phosphatase (ALP) compared to those without nausea ($123.04{\pm}69.38$ vs. $167.41{\pm}138.95$, respectively, p=0.044). Female gender correlated to a higher incidence of nausea as well (p=0.024). Patients who developed vomiting, compared to those who did not, also had lower levels (<100 IU/L) of serum ALP ($112.52{\pm}62.63$ vs. $160.10{\pm}127.80$, respectively, p=0.010), and serum alanine transferase (ALT) ($35.61{\pm}22.87$ vs. $4.97{\pm}29.62$, respectively, p=0.045). There were no statistical significances in the incidences of nausea and vomiting between male patients over 50 years old and female patients who have entered menopause (p=0.051 and p=0.409, respectively). Multivariate analysis by logistic regression analysis demonstrated that female gender and ALP>100 IU/L were the most independent predictive factors of postembolization nausea (odds ratio (OR): 3.271, 95% CI: 1.176-9.103, p=0.023 and OR: 0.447, 95% CI: 0.216-0.927, p=0.030, respectively). ALP>100 IU/L was also the most independent predictive risk factor of postembolization vomiting (OR: 0.389, 95% CI: 0.159-0.952, p=0.039). Conclusions: Postembolizaiton nausea and vomiting are common in patients with HCC. Recognition of the risk factors presented above before TACE is important for early detection and proper management of postembolization nausea and vomiting. Nevertheless, future studies are required.
The objective of this study was to assess the effects of constant high ambient temperatures on meat quality, antioxidant capacity, and carnosine expression in longissimus dorsi muscle of finishing pigs. Castrated 24 male DLY (crossbreeds between Landrace${\times}$Yorkshire sows and Duroc boars) pigs were allocated to one of three treatments: constant ambient temperature at $22^{\circ}C$ and ad libitum feeding (CON, n = 8); constant high ambient temperature at $30^{\circ}C$ and ad libitum feeding (H30, n = 8); and constant ambient temperature at $22^{\circ}C$ and pair-fed with H30 (PF, n = 8). Meat quality, malondialdehyde (MDA) content, antioxidant capacity, carnosine content, and carnosine synthetase (CARNS1) mRNA expression in longissimus dorsi muscle were measured after three weeks. The results revealed that H30 had lower $pH_{24h}$, redness at 45 min, and yellowness at 24 h post-mortem (p<0.05), and higher drip loss at 48 h and lightness at 24 h post-mortem (p<0.01). Constant heat stress disrupted the pro-oxidant/antioxidant balance in longissimus dorsi muscle with higher MDA content (p<0.01) and lower antioxidant capacity (p<0.01). Carnosine content and CARNS1 mRNA expression in longissimus dorsi muscle of H30 pigs were significantly decreased (p<0.01) after three weeks at $30^{\circ}C$. In conclusion, constant high ambient temperatures affect meat quality and antioxidant capacity negatively, and the reduction of muscle carnosine content is one of the probable reasons.
Background: It is reported that the percentage of smudge cells in the blood smear could be a prognostic indicator in chronic lymphocytic leukemia. However, the clinical significance of smudge cells in other hematological malignancies, solid tumors or non-malignant diseases is less clear. Hence, this study was conducted to survey the clinical significance of smudge cells in hematological cancers and other disorders. Materials and Methods: From January to November, 2015, the clinical data of patients who received blood examination with differential counts for clinical purpose and were found to have smudge cells in the peripheral blood film in Far Eastern Memorial Hospital were selected. The percentage of smudge cells and patient outcomes were evaluated for further univariate and survival analyses. Results: A total of 102 patients with smudge cells in their blood smears were included. Smudge cells were frequently presented in out-of-hospital cardiac arrest (OHCA; n=30), infections (n=23), hematological cancers (n=23) and solid cancers (n=10). There was no relationship between the percentage of smudge cells and the patient mortality in all diseases (OR: 1.08, 95% CI: 0.47-2.48, P=1.000) as well as the OHCA group (OR: 1.91, 95% CI: 0.38-9.60, P=0.694). It was observed that in patients with all cancers with the percentage of smudge cells less than 50% had a lower mortality rate in comparison with those who had the percentage of smudge cells of 50% or more (OR: 22.29, 95% CI: 2.38-208.80, P<0.001). Additionally, it was seemingly that patients with smudge cells of 50% or more had a lower survival rate than those with smudge cells less than 50% in all cancers with follow-up at 2-month intervals, but without statistical significance (P=0.064). Conclusions: Our survey indicated that in all cancers, those who had higher percentage of smudge cells were prone to have poor outcomes when compared with the subjects with lower percentage of smudge cells. This finding was quite different from the results of previous studies in which the race-ethnicity of most study populations was non-Asian; hence, further investigations are required. Besides, there was no apparent association of the percentage of smudge cells with patient outcomes in all diseases, including OHCA.
Background: With development and application of new and effective anti-cancer drugs, the median survival post-progression (SPP) is often prolonged, and the role of the median SPP on surrogacy performance should be considered. To evaluate the impact of the median SPP on the correlation between progression-free survival (PFS) and overall survival (OS), we performed simulations for treatment of four types of cancer, advanced gastric cancer (AGC), metastatic colorectal cancer (MCC), glioblastoma (GBM), and advanced non-small-cell lung cancer (ANSCLC). Materials and Methods: The effects of the median SPP on the statistical properties of OS and the correlation between PFS and OS were assessed. Further, comparisons were made between the surrogacy performance based on real data from meta-analyses and simulation results with similar scenarios. Results: The probability of a significant gain in OS and HR for OS was decreased by an increase of the SPP/OS ratio or by a decrease of observed treatment benefit for PFS. Similarly, for each of the four types of cancer, the correlation between PFS and OS was reduced as the median SPP increased from 2 to 12 months. Except for ANSCLC, for which the median SPP was equal to the true value, the simulated correlation between PFS and OS was consistent with the values derived from meta-analyses for the other three kinds of cancer. Further, for these three types of cancer, when the median SPP was controlled at a designated level (i.e., < 4 months for AGC, < 12 months for MCC, and <6 months for GBM), the correlation between PFS and OS was strong; and the power of OS reached 34.9% at the minimum. Conclusions: PFS is an acceptable surrogate endpoint for OS under the condition of controlling SPPs for AGC, MCC, and GBM at their limit levels; a similar conclusion cannot be made for ANSCLC.
Purpose: Chemotherapy-induced anemia (CIA) is one of the most important causes of anemia in cancer patients. This study was conducted to describe the prevalence and characteristics of CIA in solid cancer patients in the Chinese population, and to explore the relationship of white blood cell (WBC) or platelet decrease with CIA. Methods: Data on age, gender, tumor diagnosis, anti-cancer treatment and blood cell analyses were available from 220 untreated non-anemic cancer patients who received at least 2 cycles of chemotherapy, and the data were analyzed to assess their relationship with CIA or its severity. Results: 139 patients (63.2%) presented anemia, most being Grade 1 or 2. Esophageal and lung cancers were associated with a high prevalence. G3/4 leucopenia and decrease of platelets were identified as independent risk factors for the occurrence of CIA. Moreover, G3/4 leucopenia, decrease of platelet and G3/4 thrombocytopenia were found to be also associated with the severity of CIA. Cisplatin-containing regimens were a main potential factor in causing CIA, although significant association was only found on univariate analysis. Conclusion: Anemia or decrease in hematoglobin are common in Chinese cancer patients receiving chemotherapy. Cisplatin-containing regimens might be an important factor influencing the occurrence of CIA. Our analysis firstly described some risk factors, such as decrease of platelets or WBCs, severity of leucopenia or thrombocytopenia, associated with the occurrence and severity of CIA.
Background: Gastric cancer is frequently lethal despite aggressive multimodal therapies, and new treatment approaches are therefore needed. Retinoids are potential candidate drugs: they prevent cell differentiation, proliferation and malignant transformation in gastric cancer cell lines. They interact with nuclear retinoid receptors (the retinoic acid receptors [RARs] and retinoid X receptors [RXRs]), which function as transcription factors, each with three subclasses, ${\alpha}$, ${\beta}$ and ${\gamma}$. At present, little is known about retinoid expression and influence on prognosis in gastric cancers. Patients and Methods: We retrospectively analyzed the expression of the subtypes RARa, $RAR{\beta}$, $RAR{\gamma}$, RXRa, $RXR{\beta}$, $RXR{\gamma}$ by immunohistochemistry in 147 gastric cancers and 51 normal gastric epithelium tissues for whom clinical follow-up data were available and correlated the results with clinical characteristics. In addition, we quantified the expression of retinoid receptor mRNA using real-time PCR (RT-PCR) in another 6 gastric adenocarcinoma and 3 normal gastric tissues. From 2008 to 2010, 80 patients with gastric cancers were enrolled onto therapy with all-trans-retinoic acid (ATRA). Results: RARa, $RAR{\beta}$, $RAR{\gamma}$ and $RXR{\gamma}$ positively correlated with each other (p < 0.001) and demonstrated significantly lower levels in the carcinoma tissue sections (p < 0.01), with lower $RAR{\beta}$, $RAR{\gamma}$ and RXRa expression significantly related to advanced stages (p < =0.01). Tumors with poor histopathologic grade had lower levels of RARa and $RAR{\beta}$ in different histological types of gastric carcinoma (p < 0.01). Patients whose tumors exhibited low levels of RARa expression had significantly lower overall survival compared with patients who had higher expression levels of this receptor (p < 0.001, HR=0.42, 95.0% CI 0.24-0.73), and patients undergoing ATRA treatment had significantly longer median survival times (p = 0.007, HR=0.41, 95.0% CI 0.21-0.80). Conclusions: Retinoic acid receptors are frequently expressed in epithelial gastric cancer with a decreased tendency of expression and RARa may be an indicator of a positive prognosis. This study provides a molecular basis for the therapeutic use of retinoids against gastric cancer.
Objective: This study was conducted to evaluate the effects of dietary protein sources (soybean meal, SBM; low-gossypol cottonseed meal, LCSM; double-zero rapeseed meal, DRM) on laying performance, egg quality, and plasma parameters of laying hens. Methods: A total of 432 32-wk-old laying hens were randomly divided into 6 treatments with 6 replicates of 12 birds each. The birds were fed diets containing SBM, $LCSM_{100}$, or $DRM_{100}$ individually or in combination with an equal amount of crude protein (CP) ($LCSM_{50}$, $DRM_{50}$, and $LCSM_{50}-DRM_{50}$). The experimental diets, which were isocaloric (metabolizable energy, 11.11 MJ/kg) and isonitrogenous (CP, 16.5%), had similar digestible amino acid profile. The feeding trial lasted 12 weeks. Results: The daily egg mass was decreased in the $LCSM_{100}$ and $LCSM_{50}-DRM_{50}$ groups (p<0.05) in weeks 41 to 44. The $LCSM_{50}$ group did not affect egg production compared to the SBM group in weeks 41 to 44 (p>0.05) and showed increased yolk color at the end of the trial (p<0.05). Compared to the SBM group, the $LCSM_{100}$ and $LCSM_{50}-DRM_{50}$ groups showed decreased albumen weight (p<0.05), CP weight in the albumen (p<0.05) and CP weight in the whole egg (p<0.05) at 44 weeks. Plasma total protein (TP) levels were lower in the $LCSM_{100}$ group than in the SBM group at 44 weeks (p<0.05); however, TP, albumin, and globulin levels were not significantly different between the $LCSM_{50}$ group and the SBM group or between the $DRM_{50}$ group and the SBM group (p>0.05). Conclusion: Together, our results suggest that the $LCSM_{100}$ or $DRM_{100}$ diets may produce the adverse effects on laying performance and egg quality after feeding for 8 more weeks. The 100.0 g/kg LCSM diet or the 148.7 g/kg DRM diet has no adverse effects on laying performance and egg quality.
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