Efficacy and safety of apatinib combined with whole-brain radiation therapy with a simultaneous integrated boost for brain metastases from non-small cell lung cancer: a multicenter retrospective study.

Background: Brain metastases (BMs) develop in 20-65% of non-small cell lung cancer (NSCLC) patients and are associated with a poor prognosis. Apatinib, a tyrosine kinase inhibitor (TKI) that selectively inhibits the vascular endothelial growth factor receptor 2, is safe and significantly prolongs the survival of chemotherapy-refractory gastric cancer patients. This retrospective study evaluated the safety and efficacy of apatinib combined with concurrent brain radiotherapy in NSCLC patients with BMs. Methods: This trial enrolled patients with non-recurrent BM from histologically-confirmed NSCLC without any limits regarding the BM size/quantity. Eligibility criteria were patients 18-75 years old with measurable BM from histologically-confirmed NSCLC (including both newly-diagnosed and previously treated NSCLC) and expected survival time greater than 3 months. Oral apatinib (500 or 250 mg/day) was started within 1 week prior to commencing whole brain radiotherapy with simultaneous integrated boost (WBRT-SIB) and continued until one week after radiotherapy completion. In addition to toxicities, analyzed outcomes included intracranial overall response rate (iORR), intracranial disease control rate (iDCR), intracranial progression free survival (iPFS), and overall survival (OS). Results: From July 2016 to January 2020, 16 patients were enrolled in this retrospective study. After 3 months of brain radiotherapy, the iORR was 75%, the iDCR was 100%, and the brain edema index (EI) was significantly reduced compared to that before brain radiation therapy (4.2 vs. 1.9; P=0.02). The median iPFS was 16.5 months [95% confidence interval (CI): 15.1-37.4 months]. The median OS was 26 months (95% CI: 17.0-54.0 months). Most of the patients tolerated apatinib well, but 7 patients had side effects, most commonly grade 1 or 2. Only 2 patients experienced grade 3 adverse events (hypertension and oral mucositis), and no grade 4 or 5 toxicities were observed. Conclusions: Apatinib combined with WBRT-SIB appears to be safe and effective in treating BMs in NSCLC patients.

Prediction of Radiation Pneumonitis Using Genome-Scale Flux Analysis of RNA-Seq Derived From Peripheral Blood.

Purpose: Radiation pneumonitis (RP) frequently occurs during a treatment course of chest radiotherapy, which significantly reduces the clinical outcome and efficacy of radiotherapy. The ability to easily predict RP before radiotherapy would allow this disease to be avoided. Methods and Materials: This study recruited 48 lung cancer patients requiring chest radiotherapy. For each participant, RNA sequencing (RNA-Seq) was performed on a peripheral blood sample before radiotherapy. The RNA-Seq data was then integrated into a genome-scale flux analysis to develop an RP scoring system for predicting the probability of occurrence of RP. Meanwhile, the clinical information and radiation dosimetric parameters of this cohort were collected for analysis of any statistical associations between these parameters and RP. A non-parametric rank sum test showed no significant difference between the predicted results from the RP score system and the clinically observed occurrence of RP in this cohort. Results: The results of the univariant analysis suggested that the tumor stage, exposure dose, and bilateral lung dose of V5 and V20 were significantly associated with the occurrence of RP. The results of the multivariant analysis suggested that the exposure doses of V5 and V20 were independent risk factors associated with RP and a level of RP ≥ 2, respectively. Thus, our results indicate that our RP scoring system could be applied to accurately predict the risk of RP before radiotherapy because the scores were highly consistent with the clinically observed occurrence of RP. Conclusion: Compared with the standard statistical methods, this genome-scale flux-based scoring system is more accurate, straightforward, and economical, and could therefore be of great significance when making clinical decisions for chest radiotherapy.

Taxifolin Targets PI3K and mTOR and Inhibits Glioblastoma Multiforme.

Glioblastoma multiforme (GBM), the most common malignant primary brain tumor, has a very poor prognosis. With increasing knowledge of tumor molecular biology, targeted therapies are becoming increasingly integral to comprehensive GBM treatment strategies. mTOR is a key downstream molecule of the PI3K/Akt signaling pathway, integrating input signals from growth factors, nutrients, and energy sources to regulate cell growth and cell proliferation through multiple cellular responses. mTOR/PI3K dual-targeted therapy has shown promise in managing various cancers. Here, we report that taxifolin, a flavanone commonly found in milk thistle, inhibited mTOR/PI3K, promoted autophagy, and suppressed lipid synthesis in GBM. In silico analysis showed that taxifolin can bind to the rapamycin binding site of mTOR and the catalytic site of PI3K (p110α). In in vitro experiments, taxifolin inhibited mTOR and PI3K activity in five different glioma cell lines. Lastly, we showed that taxifolin suppressed tumors in mice; stimulated expression of autophagy-related genes LC3B-II, Atg7, atg12, and Beclin-1; and inhibited expression of fatty acid synthesis-related genes C/EBPα, PPARγ, FABP4, and FAS. Our observations suggest that taxifolin is potentially a valuable drug for treating GBM.

Individualized model for predicting COVID-19 deterioration in patients with cancer: A multicenter retrospective study.

The 2019 novel coronavirus has spread rapidly around the world. Cancer patients seem to be more susceptible to infection and disease deterioration, but the factors affecting the deterioration remain unclear. We aimed to develop an individualized model for prediction of coronavirus disease (COVID-19) deterioration in cancer patients. The clinical data of 276 cancer patients diagnosed with COVID-19 in 33 designated hospitals of Hubei, China from December 21, 2019 to March 18, 2020, were collected and randomly divided into a training and a validation cohort by a ratio of 2:1. Cox stepwise regression analysis was carried out to select prognostic factors. The prediction model was developed in the training cohort. The predictive accuracy of the model was quantified by C-index and time-dependent area under the receiver operating characteristic curve (t-AUC). Internal validation was assessed by the validation cohort. Risk stratification based on the model was carried out. Decision curve analysis (DCA) were used to evaluate the clinical usefulness of the model. We found age, cancer type, computed tomography baseline image features (ground glass opacity and consolidation), laboratory findings (lymphocyte count, serum levels of C-reactive protein, aspartate aminotransferase, direct bilirubin, urea, and d-dimer) were significantly associated with symptomatic deterioration. The C-index of the model was 0.755 in the training cohort and 0.779 in the validation cohort. The t-AUC values were above 0.7 within 8 weeks both in the training and validation cohorts. Patients were divided into two risk groups based on the nomogram: low-risk (total points ≤ 9.98) and high-risk (total points > 9.98) group. The Kaplan-Meier deterioration-free survival of COVID-19 curves presented significant discrimination between the two risk groups in both training and validation cohorts. The model indicated good clinical applicability by DCA curves. This study presents an individualized nomogram model to individually predict the possibility of symptomatic deterioration of COVID-19 in patients with cancer.

Survival Analysis of Radiation Therapy in Ovarian Cancer: A SEER Database Analysis.

RESULTS: A total of 20031 ovarian cancer patients were included, with 291 (1.45%) patients who received radiotherapy. The median overall survival (OS) in patients who received radiotherapy was shorter than which in patients without radiotherapy (23 vs. 75 months, P < 0.001). The Elderly, nonepithelial pathology, advanced American Joint Committee on Cancer (AJCC) stage, elevated level of CA125, and receiving radiotherapy were risk predictors to survival in both multivariable analyses before and after PSM. Among 11872 patients with III/IV stage, the radiotherapy group also showed a significantly worse prognosis (median OS: 19 vs. 44 months in patients without radiotherapy, P < 0.001). Consistent results were observed in stratification analyses on pathology and stage among patients with III/IV stage. CONCLUSIONS: For patients with ovarian cancer, radiotherapy was associated with a poor prognosis regardless of pathology or stage. Considering this is a retrospective study, future studies concerning radiotherapy combination with other new agents in ovarian cancer are needed.

Association between recent oncologic treatment and mortality among patients with carcinoma who are hospitalized with COVID-19: A multicenter study.

BACKGROUND: To the authors' knowledge, little is known regarding the association between recent oncologic treatment and mortality in patients with cancer who are infected with coronavirus disease 2019 (COVID-19). The objective of the current study was to determine whether recent oncologic treatment is associated with a higher risk of death among patients with carcinoma who are hospitalized with COVID-19. METHODS: Data regarding 248 consecutive patients with carcinoma who were hospitalized with COVID-19 were collected retrospectively from 33 hospitals in Hubei Province, China, from January 1, 2020, to March 25, 2020. The follow-up cutoff date was July 22, 2020. Univariable and multivariable logistic regression analyses were performed to identify variables associated with a higher risk of death. RESULTS: Of the 248 patients enrolled, the median age was 63 years and 128 patients (52%) were male. On admission, 147 patients (59%) did not undergo recent oncologic treatment, whereas 32 patients (13%), 25 patients (10%), 12 patients (5%), and 10 patients (4%), respectively, underwent chemotherapy, surgery, targeted therapy, and radiotherapy. At the time of last follow-up, 51 patients (21%) were critically ill during hospitalization, 40 of whom had died. Compared with patients without receipt of recent oncologic treatment, the mortality rate of patients who recently received oncologic treatment was significantly higher (24.8% vs 10.2%; hazard ratio, 2.010 [95% CI, 1.079-3.747; P = .027]). After controlling for confounders, recent receipt of chemotherapy (odds ratio [OR], 7.495; 95% CI, 1.398-34.187 [P = .015]), surgery (OR, 8.239; 95% CI, 1.637-41.955 [P = .012]), and radiotherapy (OR, 15.213; 95% CI, 2.091-110.691 [P = .007]) were identified as independently associated with a higher risk of death. CONCLUSIONS: The results of the current study demonstrated a possible association between recent receipt of oncologic treatment and a higher risk of death among patients with carcinoma who are hospitalized with COVID-19.

An online tool for predicting the prognosis of cancer patients with SARS-CoV-2 infection: a multi-center study.

PURPOSE: During the 2019 coronavirus disease (COVID-19) pandemic, oncologists face new challenges, and they need to adjust their cancer management strategies as soon as possible to reduce the risk of SARS-CoV-2 infection and tumor recurrence. However, data on cancer patients with SARS-CoV-2 infection remains scarce. METHODS: We conducted a retrospective study on 223 cancer patients with SARS-CoV-2 from 26 hospitals in Hubei, China. An individualized nomogram was constructed based on multivariate Cox analysis. Considering the convenience of the nomogram application, an online tool was also created. The predictive performance and clinical application of nomogram were verified by C-index, calibration curve and decision curve analysis (DCA). RESULTS: Among cancer patients with SARS-CoV-2, there were significant differences in clinical characteristics between survivors and non-survivors, and compared with patients with solid tumors including lung cancer, patients with hematological malignancies had a worse prognosis. Male, dyspnea, elevated PCT, increased heart rate, elevated D-dimers, and decreased platelets were risk factors for these patients. Furthermore, a good prediction performance of the online tool (dynamic nomogram: https://covid-19-prediction-tool.shinyapps.io/DynNomapp/ ) was also fully demonstrated with the C-indexes of 0.841 (95% CI 0.782-0.900) in the development cohort and 0.780 (95% CI 0.678-0.882) in the validation cohort. CONCLUSION: Overall, cancer patients with SARS-CoV-2 had unique clinical features, and the established online tool could guide clinicians to predict the prognosis of patients during the COVID-19 epidemic and to develop more rational treatment strategies for cancer patients.

Preoperative Radiotherapy Is Associated With Significant Survival Benefits for Patients With Gastric Signet Ring Cell Carcinoma: A SEER-Based Approach.

OBJECTIVE: To explore the clinical and pathological features of gastric signet ring cell carcinoma, and evaluate the survival impact of preoperative radiotherapy on these patients. METHODS: The Surveillance, Epidemiology, and End Results database was used to extract eligible patients from 2004 to 2015. The patients were divided into those with and without preoperative radiotherapy. The categorical variables were described by chi-square tests. The patients' survival was compared between the 2 groups by Kaplan-Meier method with log-rank tests. Cox proportional hazard model was adopted to identify prognostic factors of cancer-specific survival. RESULTS: Totally 4771 patients were recruited, of whom 218(4.6%) patients received preoperative radiotherapy, while 4553(95.4%) patients didn't receive this treatment. Survival analysis of the entire cohort demonstrated that preoperative radiotherapy improved both cancer-specific survival and overall survival (p < 0.001) of the patients. Cox proportional hazard models identified age >60, tumor size >50 mm, TNM stage II-IV as independent risk factors for poor prognosis (HR > 1, p < 0.05). Notably, preoperative radiotherapy was identified as an independent protective factor for favorable prognosis (HR < 1, p < 0.05). Subgroup survival analysis showed that preoperative radiotherapy exerted significant survival benefits for the stages III and IV patients. CONCLUSIONS: In this population-based study, preoperative radiotherapy is associated with significant survival benefits for the patients with advanced gastric signet ring cell carcinoma. Hence preoperative radiotherapy is feasible for these patients.

A nomogram for predicting mortality in patients with COVID-19 and solid tumors: a multicenter retrospective cohort study.

BACKGROUND: Individualized prediction of mortality risk can inform the treatment strategy for patients with COVID-19 and solid tumors and potentially improve patient outcomes. We aimed to develop a nomogram for predicting in-hospital mortality of patients with COVID-19 with solid tumors. METHODS: We enrolled patients with COVID-19 with solid tumors admitted to 32 hospitals in China between December 17, 2020, and March 18, 2020. A multivariate logistic regression model was constructed via stepwise regression analysis, and a nomogram was subsequently developed based on the fitted multivariate logistic regression model. Discrimination and calibration of the nomogram were evaluated by estimating the area under the receiver operator characteristic curve (AUC) for the model and by bootstrap resampling, a Hosmer-Lemeshow test, and visual inspection of the calibration curve. RESULTS: There were 216 patients with COVID-19 with solid tumors included in the present study, of whom 37 (17%) died and the other 179 all recovered from COVID-19 and were discharged. The median age of the enrolled patients was 63.0 years and 113 (52.3%) were men. Multivariate logistic regression revealed that increasing age (OR=1.08, 95% CI 1.00 to 1.16), receipt of antitumor treatment within 3 months before COVID-19 (OR=28.65, 95% CI 3.54 to 231.97), peripheral white blood cell (WBC) count ≥6.93 ×109/L (OR=14.52, 95% CI 2.45 to 86.14), derived neutrophil-to-lymphocyte ratio (dNLR; neutrophil count/(WBC count minus neutrophil count)) ≥4.19 (OR=18.99, 95% CI 3.58 to 100.65), and dyspnea on admission (OR=20.38, 95% CI 3.55 to 117.02) were associated with elevated mortality risk. The performance of the established nomogram was satisfactory, with an AUC of 0.953 (95% CI 0.908 to 0.997) for the model, non-significant findings on the Hosmer-Lemeshow test, and rough agreement between predicted and observed probabilities as suggested in calibration curves. The sensitivity and specificity of the model were 86.4% and 92.5%. CONCLUSION: Increasing age, receipt of antitumor treatment within 3 months before COVID-19 diagnosis, elevated WBC count and dNLR, and having dyspnea on admission were independent risk factors for mortality among patients with COVID-19 and solid tumors. The nomogram based on these factors accurately predicted mortality risk for individual patients.

Clinical features and short-term outcomes of elderly patients with COVID-19.

BACKGROUND: The outbreak of Coronavirus Disease 2019 (COVID-19) has become a global public health emergency. METHODS: 204 elderly patients (≥60 years old) diagnosed with COVID-19 in Renmin Hospital of Wuhan University from January 31st to February 20th, 2020 were included in this study. Clinical endpoint was in-hospital death. RESULTS: Of the 204 patients, hypertension, diabetes, cardiovascular disease, and chronic obstructive pulmonary disease (COPD) were the most common coexisting conditions. 76 patients died in the hospital. Multivariate analysis showed that dyspnea (hazards ratio (HR) 2.2, 95% confidence interval (CI) 1.414-3.517; p < 0.001), older age (HR 1.1, 95% CI 1.070-1.123; p < 0.001), neutrophilia (HR 4.4, 95% CI 1.310-15.061; p = 0.017) and elevated ultrasensitive cardiac troponin I (HR 3.9, 95% CI 1.471-10.433; p = 0.006) were independently associated with death. CONCLUSION: Although so far the overall mortality of COVID-19 is relatively low, the mortality of elderly patients is much higher. Early diagnosis and supportive care are of great importance for the elderly patients of COVID-19.

Adenosquamous carcinoma may have an inferior prognosis to signet ring cell carcinoma in patients with stages I and II gastric cancer.

BACKGROUND: Primary gastric adenosquamous carcinoma (ASC) is an exceedingly rare histological subtype. Gastric signet ring cell carcinoma (SRC) is a unique subtype with distinct tumor biology and clinical features. The prognosis of gastric ASC vs SRC has not been well established to date. We hypothesized that further knowledge about these distinct cancers would improve the clinical management of such patients. AIM: To investigate the clinicopathological characteristics and prognosis of gastric ASC vs SRC. METHODS: A cohort of gastric cancer patients was retrospectively collected from the Surveillance, epidemiology, and end results program database. The 1:4 propensity score matching was performed among this cohort. The clinicopathological features and prognosis of gastric ASC were compared with gastric SRC by descriptive statistics. Kaplan-Meier method was utilized to calculate the median survival of the two groups of patients. Cox proportional hazard regression models were used to identify prognostic factors. RESULTS: Totally 6063 patients with gastric ASC or SRC were identified. A cohort of 465 patients was recruited to the matched population, including 370 patients with SRC and 95 patients with ASC. Gastric ASC showed an inferior prognosis to SRC after propensity score matching. In the post-matching cohort, the median cancer specific survival was 13.0 (9.7-16.3) mo in the ASC group vs 20.0 (15.7-24.3) mo in the SRC group, and the median overall survival had a similar trend (P < 0.05). ASC and higher tumor-node-metastasis stage were independently associated with a poor survival, while radiotherapy and surgery were independent protective factors for improved prognosis. Subgroup survival analysis revealed that the prognosis of ASC was inferior to SRC only in stages I and II patients. CONCLUSION: ASC may have an inferior prognosis to SRC in patients with stages I and II gastric cancer. Our study supports radiotherapy and surgery for the future management of this clinically rare entity.

Radiotherapy for oligometastatic tumor improved the prognosis of patients with non-small cell lung cancer (NSCLC).

BACKGROUND: This study was conducted to investigate if radiotherapy improved the overall survival (OS) of patients with oligometastatic non-small cell lung cancer (NSCLC). METHODS: From January 2012 to August 2015, 323 NSCLC patients with distant metastasis were administered radiotherapy. Ninety-five patients with oligometastatic NSCLC who were sensitive to the initial chemotherapy were treated with radiotherapy for the residual lesions. Initial treatment consisted of four to six cycles of induction chemotherapy. If the patients responded to the initial treatment without developing new metastases, the residual sites were radiated at a total dose of 56-66 Gy, including the primary and metastatic sites. OS, progression-free survival, and sites of progression were assessed. The Kaplan-Meier method was used to estimate the OS and progression-free survival probabilities. RESULTS: The median survival of the whole cohort was 15 months (95% confidence interval 6-40) and the median time to progression was 11 months (95% confidence interval 4-24). Sixty-seven patients had died by the end of follow-up. The one-year and two-year OS rates were 58% and 23%, respectively. Patients progressed either with brain (n = 14), bone (n = 11), lung (n = 10), liver (n = 7), adrenal gland (n = 5), or seven other sites of metastases (n = 3). Acute grade III esophageal toxicity was observed in 17 patients (18%) and grade III pulmonary toxicity in seven patients (7%). CONCLUSION: Oligometastatic non-progressive NSCLC patients may benefit from aggressive radiotherapy to the residual lesions with acceptable toxicity after systemic chemotherapy.

Circulating Tumor Cell Detection In Epithelial Ovarian Cancer Using Dual-Component Antibodies Targeting EpCAM And FRα.

PURPOSE: Circulating tumor cell (CTC) detection methods based on epithelial cell adhesion molecule (EpCAM) have low detection rates in epithelial ovarian cancer (EOC). Meanwhile, folate receptor alpha (FRα) has high expression in EOC cells. We explored the feasibility of combining FRα and EpCAM as CTC capture targets in EOC. PATIENTS AND METHODS: EpCAM and FRα antibodies were linked to magnetic nanospheres (MNs) using the principle of carbodiimide chemistry. Blood samples from healthy donor spiked with A2780 ovarian cancer cells were used for detecting the capture rate. Ninety-five blood samples from 30 patients with EOC were used for comparing the positive rate of detection when using anti-EpCAM-MNs alone with that when using combination of anti-EpCAM-MNs and anti-FRα-MNs. Samples from 28 patients initially diagnosed with EOC and 20 patients with ovarian benign disease were used for evaluating the sensitivity and specificity of combination of anti-EpCAM-MNs and anti-FRα-MNs. RESULTS: Regression analysis between the number of recovered and that of spiked A2780 cells revealed yEpCAM = 0.535x (R2 = 0.99), yFRα = 0.901x (R2 = 0.99), and yEpCAM+FRα = 0.928x (R2 = 0.99). In mixtures of A2780 and MCF7 cells, the capture rate was 92% using the combination of anti-EpCAM-MNs and anti-FRα-MNs, exceeding the rate when using anti-EpCAM-MNs or anti-FRα-MNs alone by approximately 20% (P < 0.01). The combination of anti-EpCAM-MNs and anti-FRα-MNs showed a significantly increased positive rate of CTC detection in EOC patients compared with anti-EpCAM-MNs alone (χ2 = 14.45, P < 0.001). Sensitivity values were 0.536 and 0.75 and specificity values were 0.9 and 0.85 when using anti-EpCAM-MNs alone and when using the combination of anti-EpCAM-MNs and anti-FRα-MNs, respectively. CONCLUSION: The combination of FRα and EpCAM is feasible as a CTC capture target of CTC detection in patients with EOC.

Detecting EGFR mutations and ALK/ROS1 rearrangements in non-small cell lung cancer using malignant pleural effusion samples.

BACKGROUND: The study was conducted to evaluate the feasibility of using malignant pleural effusion (MPE) as a substitute specimen for genetic testing and to determine the significance of genetic profiling of MPE tumor cells to monitor non-small cell lung cancer (NSCLC) progression and therapeutic response. METHODS: We selected 168 NSCLC patients with MPE. We extracted MPE and enriched tumor cells using a custom-designed device. EGFR mutations and ALK/ROS1 fusions were then detected by quantitative real-time PCR, and the results were used to guide targeted therapy. We investigated drug responses through imaging. RESULTS: MPE tumor cells were detected in all patients. EGFR mutations and ALK/ROS1 rearrangements were detected in biopsy samples, treated MPE, and untreated MPE. We found that treated MPE had higher sensitivity and specificity than biopsy or untreated MPE. Among the 26 EGFR inhibitor patients, 13 showed a partial response, 7 had progressive disease, and 6 showed stable disease. Among the 16 patients that received ALK/ROS1 inhibitors, 8 had a partial response, 4 had progressive disease, and 4 showed stable disease. CONCLUSION: Our study provides a new, less invasive, and highly repeatable method of analyzing MPE tumor cells in NSCLC that facilitates precision medicine and genetic testing.

miR-196b regulates gastric cancer cell proliferation and invasion via PI3K/AKT/mTOR signaling pathway.

miR-196b plays a significant role in the regulation of tumor pathogenesis and progression by promoting tumor cell proliferation, invasion and metastasis. In order to explore the effects of miR-196b on the proliferation and invasion ability of gastric cancer cells and the involved mechanisms, in the present study the lentivirus expression vector miR-196b was constructed and transfected into the human gastric cancer cell line MKN28. The cell proliferation and invasion ability were observed and the expression of PI3K/AKT/mTOR protein and mRNA were analyzed following upregulation of the expression of miR-196b. 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) results revealed that the proliferation of MKN28 cells was notably increased following upregulation of the expression of miR-196b (P<0.01). Flow cytometry analysis demonstrated that miR-196b decreased the ratios of cells in the GO/G1 stage but increased the ratios in S and G2 stage (P<0.05). Furthermore, the cell clone formation and trans-membrane rates were increased following upregulation of the expression of miR-196b (P<0.01). The nude mouse tumor growth test revealed that tumor growth was more rapid following upregulation of the expression of miR-196b. The expression of PI3K/AKT/mTOR protein and mRNA were increased following upregulation of the expression of miR-196b. We concluded that upregulation of miR-196b promotes the proliferation and invasion ability of gastric cancer cells by regulating the PI3K/AKT/mTOR pathway.

The SNP rs931794 in 15q25.1 Is Associated with Lung Cancer Risk: A Hospital-Based Case-Control Study and Meta-Analysis.

BACKGROUND: Lung cancer is one of the most common human malignant diseases and the leading cause of cancer death worldwide. The rs931794, a SNP located in 15q25.1, has been suggested to be associated with lung cancer risk. Nevertheless, several genetic association studies yielded controversial results. METHODS AND FINDINGS: A hospital-based case-control study involving 611 cases and 1062 controls revealed the variant of rs931794 was related to increased lung cancer risk. Stratified analyses revealed the G allele was significantly associated with lung cancer risk among smokers. Following meta-analysis including 6616 cases and 7697 controls confirmed the relevance of rs931794 variant with increased lung cancer risk once again. Heterogeneity should be taken into account when interpreting the consequences. Stratified analysis found ethnicity, histological type and genotyping method were not the sources of between-study heterogeneity. Further sensitivity analysis revealed that the study "Hsiung et al (2010)" might be the major contributor to heterogeneity. Cumulative meta-analysis showed the trend was increasingly obvious with adding studies, confirming the significant association. CONCLUSIONS: Results from our current case-control study and meta-analysis offered insight of association between rs931794 and lung cancer risk, suggesting the variant of rs931794 might be related with increased lung cancer risk.

Radiation-induced pulmonary injury accelerated pulmonary metastasis in a mouse model of breast cancer.

The aim of the present study was to investigate the acceleration of pulmonary metastasis due to pulmonary injury caused by radiation treatment in a mouse model of breast cancer, in addition to determining the associated mechanism. The passive metastatic breast cancer model was used in radiation-treated BALB/c mice. In total, 24 mice were randomly separated into two groups, with 12 mice per group, and the groups were treated with or without pulmonary radiation. The survival time and variation of the weights of the lungs, spleen and liver were recorded. Lung metastasis was also evaluated, and chemokine (C-X-C motif) ligand 12 (CXCL12)/chemokine (C-X-C motif) receptor 4 (CXCR4) expression was determined. The results revealed that the group with radiation-induced pulmonary injury exhibited an increased incidence of pulmonary metastasis and shorter survival time compared with the mice without pulmonary radiation. The radiation-treated group possessed an increased number of metastatic nodules in the lungs, but metastasis was not evident in the liver and spleen. The CXCL12/CXCR4 axis was markedly expressed and the expression was significantly increased subsequent to radiation compared with the expression in normal lung tissues. The present study demonstrated that radiation-induced pulmonary injury may accelerate metastatic tumor growth and decrease the overall survival rate of the mice following in situ injection of tumor cells. Tumor localization and growth may have been favored by metastatic conditioning in the lung subsequent to radiotherapy. The CXCL12/CXCR4 axis may affect key elements in the multistep process of metastasis induced by radiation injury.

TT genotype of GNAS1 T393C polymorphism predicts better outcome of advanced non-small cell lung cancer patients.

AIM: To evaluate the potential prognostic value of GNAS1 T393C polymorphism in advanced non-small cell lung cancer. METHODS: We extracted genomic DNA from the peripheral blood leucocytes of 94 patients with advanced non-small cell lung cancer. Quantitative real-time polymerase chain reaction was used to determine the allelic discrimination. The correlation between genotype and overall survival was evaluated using the multivariate analysis and Kaplan-Meier approach. RESULTS: Thirty-eight out of 94 (40%) patients displayed a TT genotype, 29 out of 94 (31%) a CT genotype and 27 out of 94 (29%) a CC genotype. The median survival of TT (25 mo) genotype carriers was longer than CT (12 mo) or CC (8 mo) genotype carriers. The favorable TT genotype predicted better overall survival (OS) (2-year OS: 48%; P =0.01) compared with CT (2-year OS: 18%) or CC (2-year OS: 15%) genotype. However, dichotomization between C-genotypes (CC + CT) and T-genotypes (TT) revealed significantly lower survival rates (2-year OS: 16%; P = 0.01) for C allele carriers. CONCLUSION: Our data provided strong evidence that the GNAS1 T393C genetic polymorphism influenced the prognosis in advanced non-small lung cancer with a worse outcome for C allele carriers.