TP73-AS1 promotes breast cancer cell proliferation through miR-200a-mediated TFAM inhibition.

P73 antisense RNA 1T (TP73-AS1 or PDAM) is a long non-coding RNA, which can regulate apoptosis through regulation of p53 signaling-related anti-apoptotic genes. An abnormal change of TP73-AS1 expression was noticed in cancers. The effects of TP73-AS1 in breast cancer (BC) growth and the underlying mechanism remain unclear so far. In the present study, the effect of TP73-AS1 in BC cell lines and clinical tumor samples was detected so as to reveal its role and function. In the present study, TP73-AS1 was specifically upregulated in BC tissues and BC cell lines and was correlated to a poorer prognosis in patients with BC. TP73-AS1 knocking down suppressed human BC cell proliferation in vitro through regulation of TFAM. In our previous study, we demonstrated that miR-200a inhibits BC cell proliferation through targeting TFAM; here we revealed that TP73-AS1 could regulate miR-200a through direct targeting. Moreover, TP73-AS1 might compete with TFAM for miR-200a binding thus to promote TFAM expression. Data from the present study revealed that TP73-AS1 promoted BC cell proliferation through acting as a competing endogenous RNA (ceRNA) by sponging miR-200a. In conclusion, we regarded TP73-AS1 as an oncogenic lncRNA promoting BC cell proliferation and a potential target for human BC treatment.

What factors are predictive of benefit finding in women treated for non-metastatic breast cancer? A prospective study.

OBJECTIVE: Patients with breast cancer are able to gain psychological benefits from cancer diagnosis and treatment, such as a greater purpose of life and closer relationships, termed as 'benefit finding' (BF). The objective of this study was to determine the effects of sociodemographic, pathological, and psychological variables on BF in women with non-metastatic breast cancer. METHODS: A total of 404 patients with breast cancer were recruited to complete a demographic survey, a Chinese version of the Benefit Finding Scale, the Optimism-pessimism Scale, the Multidimensional Scale of Perceived Social Support, and the Cognitive Emotion Regulation Questionnaire during the first week after the confirmation of the diagnosis (T1). All participants finished the Chinese version of the Benefit Finding Scale again 6 weeks after diagnosis (T2). RESULTS: Age and education of patients, perceived social support from family, acceptance, positive reappraisal, and the baseline level of BF exhibited a positive prediction on BF. Education, pessimism, and perceived social support from family had a positive prediction and perceived social support from friends and refocus on planning had a negative prediction on the family relationship of BF. Education, perceived social support from family and friends, and the baseline level of BF had a positive prediction on the acceptance of BF. CONCLUSIONS: Perceived social support and cognitive emotion regulation strategies employed in response to breast cancer are important contributing factors to BF in women with breast cancer. In order to improve the longer-term adaptation of patients, benefit finding, either directly or via cognitive emotion regulation strategies, could be targeted for intervention.

Benefit finding predicts depressive and anxious symptoms in women with breast cancer.

PURPOSE: The aims of this study were to examine the psychometric properties of Chinese version of the Benefit Finding Scale (BFS-C) and to evaluate the effect of benefit finding on depressive and anxious symptoms in Chinese women with breast cancer. METHODS: The English version of the Benefit Finding Scale was translated and back-translated prior to its administration. At the baseline assessment (T1), 658 women with breast cancer completed a demographic form, BFS-C, and Hospital Anxiety and Depression Scale (HAD). Then, 4 weeks later (T2), all the participants finished HAD again, and the BFS-C was re-administered to 100 patients who were randomly selected from the total sample. RESULTS: The BFS-C exhibited moderate internal consistency and test-retest reliability. Five factors were extracted by principal component analysis: personal growth, worldview, family relationship, social relationship, and acceptance, and confirmatory factor analyses supported this five-factor model. Regression analyses showed that more benefit finding at T1 could predict less depressive and anxious symptoms at T2, accounting for 21.1 % and 15.3 % of variance, respectively. More worldview, family relationship, social relationship, and acceptance at T1 were associated with less depressive symptoms at T2, and more personal growth, worldview, family relationship, and acceptance at T1 were associated with less anxious symptoms at T2. CONCLUSIONS: BFS-C is of good reliability and validity, and appropriate for assessing benefit finding in women with breast cancer. Worldview, family relationship, and acceptance are important contributing factors to depressive and anxious symptoms, which may be beneficial for women with breast cancer.

Cognitive emotion regulation strategies as predictors of depressive symptoms in women newly diagnosed with breast cancer.

OBJECTIVE: This study aimed to determine the effects of cognitive emotion regulation strategies on depressive symptoms in women with breast cancer. METHODS: Five hundred and nine women with breast cancer completed a demographic survey, the Chinese version of Cognitive Emotion Regulation Questionnaire (CERQ-C), and the Center for Epidemiological Studies Depression Scale (CES-D) at the initial assessment (T1). One month later (T2), 504 patients completed the CES-D. Patients were assigned to four groups: H-H (CES-D scores ≥16 at both timepoints), H-L (CES-D score ≥16 at T1, <16 at T2), L-H (CES-D score <16 at T1, ≥16 at T2) and L-L (CES-D scores <16 at both timepoints). RESULTS: Over 80% patients had mild or no depressive symptoms at both timepoints. There were significant group differences in cognitive emotion regulation strategies. CERQ-C subscale scores for adaptive strategies were higher, and scores for maladaptive strategies were lower among patients in L-L and H-L groups than among those in H-H group. Hierarchical regression analyses showed that cognitive emotion regulation strategies at T1 differentiated depressive symptoms at T2, accounting for 56.5% of variance after controlling for sociodemographic and biological variables and baseline levels of depression. Greater acceptance, positive refocusing, and positive reappraisal at T1 were associated with fewer depressive symptoms at T2. CONCLUSIONS: Cognitive emotion regulation strategies accounted for considerable variance in depressive symptom scores 1 month later. The strategies of acceptance, positive refocusing, and positive reappraisal may be beneficial for women with breast cancer. Intervention studies are needed to confirm if these associations are causal.

[Psychometric features of the body image after breast cancer questionnaire-Chinese version in women with breast cancer].

OBJECTIVE: To examine the psychometric features of the body image after breast cancer questionnaire-Chinese version (BIBCQ-C) in Chinese women with breast cancer. METHODS: A total of 545 women with breast cancer received a demographics investigation: BIBCQ-C and hospital anxiety and depression scale (HAD). Four weeks later, 31 patients were selected randomly to finish BIBCQ-C again. RESULTS: The Cronbach's alpha coefficient for the total scale was 0.90, and that for the 6 factors ranged from 0.62 to 0.87. The mean inter-item correlation coefficient of the total scale was 0.16, and the mean inter-item correlation coefficient of the subscales ranged from 0.21 to 0.57, and the test-retest reliability of the total scale and 6 factors was over 0.60. The confirmatory factor analyses supported the 6-factor model, and BIBCQ-C were significantly correlated with the symptom scales of anxiety and depression (r=0.20, 0.21, P<0.01). CONCLUSION: BIBCQ-C is reliable and valid, which can effectively assess body image of Chinese women with breast cancer.

MicroRNA-375 targets PAX6 and inhibits the viability, migration and invasion of human breast cancer MCF-7 cells.

[This retracts the article DOI: 10.3892/etm.2017.4593.].

miR-937-5p targets SOX17 to modulate breast cancer cell cycle and cell proliferation through the Wnt signaling pathway.

Breast cancer is one of the most frequent cancers in women and the globally leading cause of cancer-related deaths. Bioinformatics and experimental analyses found that miR-937-5p may play a proto-oncogenic role in breast cancer; however, the specific effects and the molecular mechanism need further investigation. GSEA-KEGG and GSEA-GO suggested that miR-937-5p might be related to cell cycle and DNA replication. The experimental data indicated that miR-937-5p inhibition significantly repressed the proliferation of breast carcinoma cells and elicited S-phase cell cycle arrest. Meanwhile, the protein levels of proliferating marker ki-67 and cell cycle regulators Cyclin A2, Cyclin B1, CDK1, and Cyclin D1 were also decreased by miR-937-5p inhibition. miR-937-5p could directly bind to and negatively regulate SOX17. SOX17 overexpression also significantly repressed the proliferation of breast carcinoma cells and elicited S-phase cell cycle arrest and decreased ki-67, ß-catenin, c-Myc, Cyclin A2, Cyclin B1, Cyclin D1, and CDK1 protein contents. More importantly, the effects of miR-937-5p were reversed by SOX17.

Corrigendum: Effectiveness and Safety of Pyrotinib, and Association of Biomarker With Progression-Free Survival in Patients With HER2-Positive Metastatic Breast Cancer: A Real-World, Multicentre Analysis.

[This corrects the article DOI: 10.3389/fonc.2020.00811.].

Pyrotinib Treatment in Patients With HER2-positive Metastatic Breast Cancer and Brain Metastasis: Exploratory Final Analysis of Real-World, Multicenter Data.

PURPOSE: Patients with HER2-positive (HER2+) metastatic breast cancer (MBC) have poor prognoses. Pyrotinib has shown promising antitumor activity in MBC to improve progression-free survival (PFS). However, findings based on real-world data to analyze whether pyrotinib affects overall survival (OS) remain scarce. EXPERIMENTAL DESIGN: This real-world study is an exploratory analysis of brain metastasis (BM) and the final update of our preceding study of 168 patients with HER2+ MBC. PFS, OS, tumor mutation burden (TMB), clinical benefit rate (CBR), and overall response rate (ORR) were analyzed. RESULTS: Pyrotinib treatment led to a median PFS time of 8.00 months and a median OS of 19.07 months in the 168 participants. High TMB was associated with poor OS (P = 0.0072) and PFS (P = 0.0028). In the 39 patients with BM, the median PFS and OS were 8.67 and 13.93 months, respectively. The surgery/radiation (S/R) group of patients with BM had prolonged survival (PFS: 9.97 vs. 7.73 months P = 0.19; OS: 20.67 vs. 12.43 months P = 0.021) compared with the no surgery/no radiation group (NS/NR). The CBR was 58.6% (S/R) vs. 41.4% (NS/NR), while the ORR was 24.1% (S/R) vs. 31.0% (NS/NR). CONCLUSIONS: Pyrotinib shows promise as a novel pan-HER2 tyrosine kinase inhibitor (TKI) for the treatment of BM and should be evaluated further. Surgical or radiotherapy in combination with pyrotinib was found to statistically improve OS in our cohort. TMB could be an exploratory biomarker for predicting PFS and OS, but its clinical application still needs further verification.

[Expression of galectin-3 and Sambucus nigra agglutinin and its clinicopathological significance in benign and malignant lesions of breast].

OBJECTIVE: To detect the expression of galectin-3 (gal-3) and Sambucus nigra agglutinin (SNA) and determine their clinicopathological significance in breast cancers and benign breast lesions. METHODS: Envison immunohistochemistry for staining gal-3 expression, and ABC affinity-cytochemistry to detect SNA expression were used in paraffin-embedded slides from specimens of breast cancers (n=60) and benign lesions (n=30). RESULTS: The positive rates and scoring means of gal-3 and SNA were significantly higher in breast cancer (48.3%, 2.07 +/- 2.25, 2.12 +/- 2.26) than those in benign lesions (26.7%, 1.03 +/- 1.63, 1.07 +/- 1.59, P < 0.05). The scoring means of gal-3 and SNA expression were significantly lower in the positive cases of estrogen receptor (ER) and the negative ones of CA15-3 than those in the negative cases and the positive ones (P < 0.05).The survival analysis of Kaplan-Meier showed the 5-year survival rate and mean survival period were significantly lower in the gal-3 or SNA expression positive cases than those in the negative cases of breast cancer (P<0.01). CONCLUSION: The expressive level of gal-3 and SNA lectins might have important effect on the carcinogenesis, progression and biologic behaviors of breast cancer. The positive cases of gal-3 and /or SNA expression might have poor prognosis.

[Expression of GRP78 and GRP94 in the liver tissues and their clinicopathological significance in children with hepatoblastoma].

OBJECTIVE: To study the expression of glucose-regulated protin 78 (GRP78) and glucose-regulated protin 94 (GRP94) in the liver tissues from children with hepatoblastoma (HB) and to investigate the possible clinicopathological values of GRP78 and GRP94 in HB. METHODS: Liver tissue specimens from 15 children with HB and 10 specimens of normal liver tissues were obtained. EnVison immunohistochemistry was used to detect the expression of GRP78 and GRP94 in the conventional paraffin-embedded liver sections. RESULTS: The positive rates of GRP78 expression (53% vs 10%; P<0.05) and GRP94 expression (60% vs 10%; P<0.05) in HB liver tissues were significantly higher than those in the normal liver tissues. The positive rates of GRP78 expression in the cases without lymphnode metastasis or in clinical stage I-II were significantly lower than those in the cases with lymphnode metastasis or in clinical stage III-IV (P<0.05). GRP94 showed a decreased tendency of positive expression in the cases without lymphnode metastasis or in clinical stage I-II when compared with the cases with lymphnode metastasis or in clinical stage III-IV, although there were no statistical differences between them. CONCLUSIONS: GRP78 and GRP94 expression might play important roles in the pathogenesis and progression of pediatric HB.

Effectiveness and Safety of Pyrotinib, and Association of Biomarker With Progression-Free Survival in Patients With HER2-Positive Metastatic Breast Cancer: A Real-World, Multicentre Analysis.

Background: Pyrotinib, an irreversible pan-ERBB inhibitor, has shown promising antitumour activity, and acceptable tolerability. This research was conducted to evaluate the actual use and effectiveness of pyrotinib in China, therefore, contributed to solve the problem of real-world data scarcity. Methods: In this retrospective study, 168 patients who received pyrotinib treatment for HER2-positive metastatic breast cancer (MBC) in Hunan Province from June 2018 to August 2019 were included. Progression-free survival (PFS), tumor mutation burden (TMB), and drug-related adverse events (AEs) after pyrotinib administration were analyzed. Results: The median PFS (mPFS) time in the 168 participants was 8.07 months. The mPFS times in patients with pyrotinib in second-line therapy (n = 65) and third-or-higher-line therapy (n = 94) were 8.10 months and 7.60 months, respectively. Patients with brain metastases achieved 8.80 months mPFS time. In patients with pyrotinib in third-or-higher-line therapy, patients who had previously used lapatinib still got efficacy but showed a shorter mPFS time (6.43 months) than patients who had not (8.37 months). TMB was measured in 28 patients, K-M curve (P = 0.0024) and Multivariate Cox analysis (P = 0.0176) showed a significant negative association between TMB and PFS. Diarrhea occurred in 98.2% of participants (in any grade) and 19.6% in grade 3-4 AEs. Conclusion: Pyrotinib is highly beneficial to second-or-higher-line patients or HER2-positive MBC patients with brain metastases. Pyrotinib seems to be a feasible strategy both in combination of chemotherapeutic drugs or as a replacement of lapatinib if diseases progressed. TMB could be a potential predictor for evaluating pyrotinib's effectiveness in HER2-positive MBC.

MicroRNA-375 targets PAX6 and inhibits the viability, migration and invasion of human breast cancer MCF-7 cells.

MicroRNAs (miRs) are a type of small non-coding RNA that serve crucial roles in the development and progression of breast cancer. However, the exact role and underlying molecular mechanism of miR-375 in mediating the growth and metastasis of breast cancer remains unknown. In the present study, reverse transcription-quantitative polymerase chain reaction and western blot analysis were conducted to examine RNA and protein expression. A luciferase reporter assay was performed to determine the association between miR-375 and paired box 6 (PAX6). The results of the current study indicate that the expression of miR-375 was reduced in breast cancer tissues compared with matched adjacent normal tissues. Transfection with miR-375 mimics led to a significant increase in levels of miR-375 in human breast cancer Michigan Cancer Foundation (MCF)-7 cells (P<0.05). The increase in miR-375 expression caused a significant decrease in the viability, migration and invasion of MCF-7 cells (P<0.05), accompanied by a reduced expression of matrix metalloproteinase (MMP) 2 and MMP9 proteins. Luciferase reporter assay identified PAX6 as a novel target of miR-375 and miR-375 in turn, negatively regulated the protein expression of PAX6 in MCF-7 cells. By contrast, overexpression of PAX6 led to a significant increase in MCF-7 cell viability (P<0.01) but did not affect the migration and invasion of MCF-7 cells, suggesting that the inhibitory effect of miR-375 on MCF-7 cell viability may be occurring, in part, via the direct targeting of PAX6.

Subgroup Economic Evaluation of Radiotherapy for Breast Cancer After Mastectomy.

BACKGROUND: A recent meta-analysis by the Early Breast Cancer Trialists' Collaborative Group found significant improvements achieved by postmastectomy radiotherapy (PMRT) for patients with breast cancer with 1 to 3 positive nodes (pN1-3). It is unclear whether PMRT is cost-effective for subgroups of patients with positive nodes. OBJECTIVE: To determine the cost-effectiveness of PMRT for subgroups of patients with breast cancer with positive nodes. METHODS: A semi-Markov model was constructed to estimate the expected lifetime costs, life expectancy, and quality-adjusted life-years for patients receiving or not receiving radiation therapy. Clinical and health utilities data were from meta-analyses by the Early Breast Cancer Trialists' Collaborative Group or randomized clinical trials. Costs were estimated from the perspective of the Chinese society. One-way and probabilistic sensitivity analyses were performed. FINDINGS: The incremental cost-effective ratio was estimated as $7984, $4043, $3572, and $19,021 per quality-adjusted life-year for patients with positive nodes (pN+), patients with pN1-3, patients with pN1-3 who received systemic therapy, and patients with >4 positive nodes (pN4+), respectively. According to World Health Organization recommendations, these incremental cost-effective ratios were judged as cost-effective. However, the results of one-way sensitivity analyses suggested that the results were highly sensitive to the relative effectiveness of PMRT (rate ratio). IMPLICATIONS: We determined that the results were highly sensitive to the rate ratio. However, the addition of PMRT for patients with pN1-3 in China has a reasonable chance to be cost-effective and may be judged as an efficient deployment of limited health resource, and the risk and uncertainty of PMRT are relatively greater for patients with pN4+.

[Difference in expression of VEGF, bFGF and their receptors between the young and postmenopausal women with breast cancer].

OBJECTIVE: To study the difference in the expression of VEGF, bFGF and their receptors between young and postmenopausal women with breast cancer. METHODS: The expression of VEGF, FLK-1, bFGF and FLG in 40 young and 30 postmenopausal women with breast cancer was studied by immunohistochemical method (SABC), with its relation with axillary lymph node metastasis and the clinical and pathologic characteristics. The expression index between these two groups was compared. RESULTS: The positive axillary lymph node rate and the mean expression of VEGF, bFGF in the young group were higher than postmenopausal group (P < 0.01 and P < 0.05), respectively. The mean expression of VEGF, bFGF, FLK-1 and FLG of axillary lymph node positive patients was higher than the negative ones both in young and postmenopausal women groups (P < 0.05 and P < 0.01). There was also a significant difference in VEGF, bFGF, FLK-1, FLG and MVC between the stage 0 - II and stage III - IV (P < 0.05 and P < 0.01) in both groups. CONCLUSION: Breast cancer angiogenesis, characterized by the high expression of VEGF and bFGF, is directly correlated with the high tumor aggressiveness in the young women.

Proteomic analysis reveals that MAEL, a component of nuage, interacts with stress granule proteins in cancer cells.

The Maelstrom (MAEL) gene is a cancer-testis (or cancer-germline) gene, which is predominantly expressed in germline cells under normal conditions, but is aberrantly expressed in a range of human cancer cells. In germline cells, MAEL is found predominantly in the nuage, where it plays an essential role in piRNA biogenesis and piRNA-mediated silencing of transposons. However, the role of MAEL in cancer has not been elucidated. We performed immunoprecipitation and Nano-LC-MS/MS analysis to investigate the interactome of MAEL, and identified 14 components of stress granules (SGs) as potential binding partners of MAEL in MDA-MB-231 human breast cancer and SW480 colorectal cancer cells. The interactions between MAEL and 8 of these SG components (PABPC1, YBX1, KHSRP, SYNCRIP, DDX39, ELAV1, EIF4A1 and EIF3F) were confirmed by anti-tag immunoprecipitation. Immunofluorescence analysis showed that MAEL co-localizes with the SG marker PABPC1 in SGs during oxidative stress. Nuages and SGs are the cytoplasmic RNA granules of germline cells and stressed somatic cells, respectively, and both serve as a platform for small RNA-mediated gene silencing. It is, therefore, suggested that MAEL may be involved in miRNA-mediated gene silencing in SGs, as it does in the nuage. This finding should be valuable toward understanding the function of MAEL in carcinogenesis.

Economic outcomes of maintenance gefitinib for locally advanced/metastatic non-small-cell lung cancer with unknown EGFR mutations: a semi-Markov model analysis.

BACKGROUND: Maintenance gefitinib significantly prolonged progression-free survival (PFS) compared with placebo in patients from eastern Asian with locally advanced/metastatic non-small-cell lung cancer (NSCLC) after four chemotherapeutic cycles (21 days per cycle) of first-line platinum-based combination chemotherapy without disease progression. The objective of the current study was to evaluate the cost-effectiveness of maintenance gefitinib therapy after four chemotherapeutic cycle's stand first-line platinum-based chemotherapy for patients with locally advanced or metastatic NSCLC with unknown EGFR mutations, from a Chinese health care system perspective. METHODS AND FINDINGS: A semi-Markov model was designed to evaluate cost-effectiveness of the maintenance gefitinib treatment. Two-parametric Weibull and Log-logistic distribution were fitted to PFS and overall survival curves independently. One-way and probabilistic sensitivity analyses were conducted to assess the stability of the model designed. The model base-case analysis suggested that maintenance gefitinib would increase benefits in a 1, 3, 6 or 10-year time horizon, with incremental $184,829, $19,214, $19,328, and $21,308 per quality-adjusted life-year (QALY) gained, respectively. The most sensitive influential variable in the cost-effectiveness analysis was utility of PFS plus rash, followed by utility of PFS plus diarrhoea, utility of progressed disease, price of gefitinib, cost of follow-up treatment in progressed survival state, and utility of PFS on oral therapy. The price of gefitinib is the most significant parameter that could reduce the incremental cost per QALY. Probabilistic sensitivity analysis indicated that the cost-effective probability of maintenance gefitinib was zero under the willingness-to-pay (WTP) threshold of $16,349 (3 × per-capita gross domestic product of China). The sensitivity analyses all suggested that the model was robust. CONCLUSIONS: Maintenance gefitinib following first-line platinum-based chemotherapy for patients with locally advanced/metastatic NSCLC with unknown EGFR mutations is not cost-effective. Decreasing the price of gefitinib may be a preferential choice for meeting widely treatment demands in China.

Cost-effectiveness of continuation maintenance pemetrexed after cisplatin and pemetrexed chemotherapy for advanced nonsquamous non-small-cell lung cancer: estimates from the perspective of the Chinese health care system.

BACKGROUND: Continuation maintenance treatment with pemetrexed is approved by current clinical guidelines as a category 2A recommendation after induction therapy with cisplatin and pemetrexed chemotherapy (CP strategy) for patients with advanced nonsquamous non-small-cell lung cancer (NSCLC). However, the cost-effectiveness of the treatment remains unclear. OBJECTIVE: We completed a trial-based assessment, from the perspective of the Chinese health care system, of the cost-effectiveness of maintenance pemetrexed treatment after a CP strategy for patients with advanced nonsquamous NSCLC. METHODS: A Markov model was developed to estimate costs and benefits. It was based on a clinical trial that compared continuation maintenance pemetrexed therapy plus best supportive care (BSC) versus placebo plus BSC after a CP strategy for advanced nonsquamous NSCLC. Sensitivity analyses were conducted to assess the stability of the model. RESULTS: The model base case analysis suggested that continuation maintenance pemetrexed therapy after a CP strategy would increase benefits in a 1-, 2-, 5-, or 10-year time horizon, with incremental costs of $183,589.06, $126,353.16, $124,766.68, and $124,793.12 per quality-adjusted life-year gained, respectively. The most sensitive influential variable in the cost-effectiveness analysis was the utility of the progression-free survival state, followed by proportion of patients with postdiscontinuation therapy in both arms, proportion of BSC costs for PFS versus progressed survival state, and cost of pemetrexed. Probabilistic sensitivity analysis indicated that the cost-effective probability of adding continuation maintenance pemetrexed therapy to BSC was zero. One-way and probabilistic sensitivity analyses revealed that the Markov model was robust. CONCLUSIONS: Continuation maintenance of pemetrexed after a CP strategy for patients with advanced nonsquamous NSCLC is not cost-effective based on a recent clinical trial. Decreasing the price or adjusting the dosage of pemetrexed may be a better option for meeting the treatment demands of Chinese patients.

Economic evaluation of first-line adjuvant chemotherapies for resectable gastric cancer patients in China.

BACKGROUND: First-line postoperative adjuvant chemotherapies with S-1 and capecitabine and oxaliplatin (XELOX) were first recommended for resectable gastric cancer patients in the 2010 and 2011 Chinese NCCN Clinical Practice Guidelines in Oncology: Gastric Cancer; however, their economic impact in China is unknown. OBJECTIVE: The aim of this study was to compare the cost-effectiveness of adjuvant chemotherapy with XELOX, with S-1 and no treatment after a gastrectomy with extended (D2) lymph-node dissection among patients with stage II-IIIB gastric cancer. METHODS: A Markov model, based on data from two clinical phase III trials, was developed to analyse the cost-effectiveness of patients in the XELOX group, S-1 group and surgery only (SO) group. The costs were estimated from the perspective of Chinese healthcare system. The utilities were assumed on the basis of previously published reports. Costs, quality-adjusted life-years (QALYs) and incremental cost-effectiveness ratios (ICER) were calculated with a lifetime horizon. One-way and probabilistic sensitivity analyses were performed. RESULTS: For the base case, XELOX had the lowest total cost ($44,568) and cost-effectiveness ratio ($7,360/QALY). The relative scenario analyses showed that SO was dominated by XELOX and the ICERs of S-1 was $58,843/QALY compared with XELOX. The one-way sensitivity analysis showed that the most influential parameter was the utility of disease-free survival. The probabilistic sensitivity analysis predicted a 75.8% likelihood that the ICER for XELOX would be less than $13,527 compared with S-1. When ICER was more than $38,000, the likelihood of cost-effectiveness achieved by S-1 group was greater than 50%. CONCLUSIONS: Our results suggest that for patients in China with resectable disease, first-line adjuvant chemotherapy with XELOX after a D2 gastrectomy is a best option comparing with S-1 and SO in view of our current study. In addition, S-1 might be a better choice, especially with a higher value of willingness-to-pay threshold.

X-ray repair cross-complementing group 1(XRCC1) genetic polymorphisms and thyroid carcinoma risk: a meta-analysis.

A number of studies have been conducted to explore the association of XRCC1 polymorphisms with thyroid cancer risk, but the results have been inconsistent. Thus we performed the present meta-analysis to clarify this issue based on all of the evidence available to date. Relevant studies were retrieved by searching PubMed and statistical analysis conducted using Stata software. Nine studies were included in this meta-analysis (1,620 cases and 3,557 controls). There were 6 studies (932 cases and 2,270 controls) of the Arg194Trp polymorphism, 7 studies (1432 cases and 3356 controls) of the Arg280His polymorphism and 9 studies (1,620 cases and 3,557 controls) for the Arg399Gln polymorphism. No association of XRCC1 Arg194Trp, Arg280His and Arg399Gln polymorphism with thyroid cancer risk was observed in the overall analysis. However, subgroup analysis revealed: 1) an elevated risk in aa vs AA analysis (OR=2.03, 95%CI= 1.24-3.31) and recessive genetic model analysis (OR=1.93, 95%CI= 1.20-3.08) in the larger sample size trials for XRCC1 Arg194Trp polymorphism; 2) a decreased thyroid cancer risk on subgroup analysis based on ethnicity in Aa vs AA analysis (OR=0.84, 95%CI= 0.72-0.98) and in a dominant genetic model (OR=0.84, 95%CI= 0.72-0.97) in Caucasian populations for the XRCC1 Arg399Gln polymorphism; 3) a decreased thyroid cancer risk on subgroup analysis based on design type in Aa vs AA analysis (OR=0.72, 95% CI= 0.54-0.97) among the PCC trials for the Arg399Gln polymorphism. Our results suggest that the XRCC1 Arg399Gln polymorphism may be associated with decreased thyroid cancer risk among Caucasians and XRCC1 Arg194Trp may be associated with a tendency for increased thyroid cancer risk in the two larger sample size trials.