Dopamine D2 receptors in the dorsomedial prefrontal cortex modulate social hierarchy in male mice.

Social hierarchy greatly influences behavior and health. Both human and animal studies have signaled the medial prefrontal cortex (mPFC) as specifically related to social hierarchy. Dopamine D1 receptors (D1Rs) and D2 receptors (D2Rs) are abundantly expressed in the mPFC, modulating its functions. However, it is unclear how DR-expressing neurons in the mPFC regulate social hierarchy. Here, using a confrontation tube test, we found that most adult C57BL/6J male mice could establish a linear social rank after 1 week of cohabitation. Lower rank individuals showed social anxiety together with decreased serum testosterone levels. D2R expression was significantly downregulated in the dorsal part of mPFC (dmPFC) in lower rank individuals, whereas D1R expression showed no significant difference among the rank groups in the whole mPFC. Virus knockdown of D2Rs in the dmPFC led to mice being particularly prone to lose the contests in the confrontation tube test. Finally, simultaneous D2R activation in the subordinates and D2R inhibition in the dominants in a pair switched their dominant-subordinate relationship. The above results indicate that D2Rs in the dmPFC play an important role in social dominance. Our findings provide novel insights into the divergent functions of prefrontal D1Rs and D2Rs in social dominance, which may contribute to ameliorating social dysfunctions along with abnormal social hierarchy.

Increased Lactobacillus Abundance Contributes to Stress Resilience in Mice Exposed to Chronic Social Defeat Stress.

INTRODUCTION: Accumulating evidence indicates that abnormalities in the composition of gastrointestinal (GI) microbiota play a vital role in stress-related disorders. Both human beings and animals perceive stressful events differently, i.e., resilience or susceptibility. However, the role of GI microbiota in stress resilience/susceptibility and the underlying mechanisms remain largely unknown. METHODS AND RESULTS: Sixty male C57BL/6J mice were exposed to 10-day chronic social defeat stress (CSDS), and 28 were found to be resilient to CSDS. We next analyzed microbiota compositions in the cecum using 16S rDNA gene sequencing, which revealed a significant increase in the relative abundance of Lactobacillus at the genus level in the resilient mice. In subsequent experiments, we found that oral administration of a strain of Lactobacillus (Lactobacillus murinus) for 2 weeks attenuated the increased levels of stress-induced corticosterone and anxiety-like behavior in stress-susceptible mice. The mRNA expression of tryptophan hydroxylase 2 (a rate-limiting enzyme in serotonin [5-HT] synthesis) was also significantly increased in the dorsal raphe nucleus (DR) of stress-susceptible mice. CONCLUSIONS: Lactobacillus contributes to stress resilience, and the DR 5-HT system may play an important role during this process. The above results suggest that certain organisms in the GI tract may play an essential role in stress response and be useful in the prevention and treatment of some stress-related psychiatric disorders, such as depression.

mGlu2/3 receptors within the ventral part of the lateral septal nuclei modulate stress resilience and vulnerability in mice.

Resilience refers to the ability to withstand or recover quickly from difficult conditions. Identification of the neurobiological mechanisms underlying resilience offers a novel way to the prevention and treatment of stress-induced psychiatric disorders such as depression. The septal nuclei have been described as an important node in emotional regulations. Metabotropic glutamate receptors (mGluRs) are abundantly expressed within the septum and play important regulatory roles in its neural activity. In this study, we assessed the functional roles of the mGlu2/3Rs and mGlu5Rs within different subregions of the septum in modulating stress resilience and vulnerability by using chronic social defeat stress (CSDS) paradigms in C57BL/6J male mice. Our results showed that approximately 47.9% of subjects exhibited anxiety- or depression-like behaviors after exposure to CSDS. The susceptible mice showed higher c-Fos expression in the lateral septal nucleus after confronted with an attacker. Compared with the resilient and control groups, the expression of mGlu2/3Rs was significantly down-regulated in the ventral part of lateral septal nucleus (LSv), but the expression of mGlu5Rs showed no significant difference among the three groups in the whole septum. Finally, we found the stress-induced social withdrawal symptoms could be rapidly relieved by intra-LSv injection of LY379268, an mGlu2/3Rs' agonist. Our findings point to an important role for mGlu2/3Rs in the LSv in promoting stress resilience and may provide potential new therapeutic targets for stress-induced psychiatric disorders, such as anxiety and depression.

mGlu2/3 receptor in the prelimbic cortex is implicated in stress resilience and vulnerability in mice.

Resilience, referring to "achieving a positive outcome in the face of adversity", is a common phenomenon in daily life. Elucidating the mechanisms of stress resilience is instrumental to developing more effective treatments for stress-related psychiatric disorders such as depression. Metabotropic glutamate receptors (mGlu2/3 and mGlu5) within the medial prefrontal cortex (mPFC) have been recently recognized as promising therapeutic targets for rapid-acting antidepressant treatment. In this study, we assessed the functional roles of the mGlu2/3 and mGlu5 within different subregions of the mPFC in modulating stress resilience and vulnerability by using chronic social defeat stress (CSDS) paradigms in mice. Our results showed that approximately 51.6% of the subjects exhibited depression- or anxiety-like behaviors after exposure to CSDS. When a susceptible mouse was confronted with an attacker, c-Fos expression in the prelimbic cortex (PrL) subregion of the mPFC substantially increased. Compared with the resilient and control groups, the expression of mGlu2/3 was elevated in the PrL of the susceptible group. The expression of mGlu5 showed no significant difference among the three groups in the whole mPFC. Finally, we found that the social avoidance symptoms of the susceptible mice were rapidly relieved by intra-PrL administration of LY341495-an mGluR2/3 antagonists. The above results indicate that mGluR2/3 within the PrL may play an important regulatory role in stress-related psychiatric disorders. Our results are meaningful, as they expand our understanding of stress resilience and vulnerability which may open an avenue to develop novel, personalized approaches to mitigate depression and promote stress resilience.

The GABA(B1) receptor within the infralimbic cortex is implicated in stress resilience and vulnerability in mice.

Resilience is the capacity to maintain normal psychological and physical functions in the face of stress and adversity. Understanding how one can develop and enhance resilience is of great relevance to not only promoting coping mechanisms but also mitigating maladaptive stress responses in psychiatric illnesses such as depression. Preclinical studies suggest that GABA(B) receptors (GABA(B1) and GABA(B2)) are potential targets for the treatment of major depression. In this study, we assessed the functional role of GABA(B) receptors in stress resilience and vulnerability by using a chronic unpredictable stress (CUS) model in mice. As the medial prefrontal cortex (mPFC) plays a key role in the top-down modulation of stress responses, we focused our study on this brain structure. Our results showed that only approximately 41.9% of subjects exhibited anxiety- or despair-like behaviors after exposure to CUS. The vulnerable mice showed higher c-Fos expression in the infralimbic cortex (IL) subregion of the mPFC when exposed to a social stressor. Moreover, the expression of GABA(B1) but not GABA(B2) receptors was significantly downregulated in IL subregion of susceptible mice. Finally, we found that intra-IL administration of baclofen, a GABA(B) receptor agonist, rapidly relieved the social avoidance symptoms of the "stress-susceptible" mice. Taken together, our results show that the GABA(B1) receptor within the IL may play an important role in stress resilience and vulnerability, and thus open an avenue to develop novel, personalized approaches to promote stress resilience and treat stress-related psychiatric disorders.

GABA(B) receptors within the lateral habenula modulate stress resilience and vulnerability in mice.

Resilience means "the ability to withstand or recover quickly in the face of adversity". Elucidating the neural and molecular mechanisms underlying stress resilience will facilitate the development of more effective treatments for stress-induced psychiatric disorders such as depression. The habenular nuclei, which consist of the medial and lateral sub-regions (MHb and LHb, respectively), have been described as a critical node in emotional regulations. GABA(B) receptors play an important regulatory role in habenular activity. In this study, we assessed the functional role of GABA(B) receptors within the habenula in stress resilience and vulnerability by using chronic social defeat stress (CSDS) model in C57BL/6 male mice. Approximately 47.1% of mice exhibited depression- or anxiety-like behaviors after exposure to CSDS. The vulnerable mice presented elevated c-Fos expression in the LHb when confronted with an attacker. On the other hand, the expression of GABA(B) receptors, including both GABA(B1) and GABA(B2) subunits, was significantly down-regulated in the LHb of the susceptible mice. Finally, we found the stress-induced social withdrawal symptoms could be rapidly relieved by intra-LHb injection of both baclofen and CGP36216 (a GABA(B) receptor agonist and antagonist respectively). The above results indicated that GABA(B) receptors in the LHb may play an important role in stress resilience and vulnerability, and thus, may be an important therapeutic target for treatments of stress-induced psychiatric disorders.

Difference in survival between right- versus left-sided colorectal neuroendocrine neoplasms.

Neuroendocrine neoplasms (NENs) are a heterogeneous group of tumors that arise from neuroendocrine cells, and in some cases are capable of producing agents that may cause characteristic hormonal syndromes (Cives and Strosberg, 2018). Such tumors were previously thought to be rare, but the rate of detection of NENs, especially from the gastrointestinal tract, is increasing with the widespread use of colonoscopy, cross-sectional imaging, and biomarkers (Gu et al., 2019). A study based on the Surveillance, Epidemiology, and End Results (SEER) database showed that the age-adjusted incidence of NENs increased 6.4-fold from 1973 (1.09 per 100 000) to 2012 (6.98 per 100 000) (Dasari et al., 2017), while there was a progressive increase in the incidence of colorectal NENs (Starzynska et al., 2017).

The underlying microbial mechanism of epizootic rabbit enteropathy triggered by a low fiber diet.

Epizootic rabbit enteropathy (ERE) is reproduced successfully in the present study by feeding rabbits a low-fibre diet, and high-throughput sequencing and quantitative real-time PCR (qPCR) analysis were applied to examine the microbial variations in the stomach, small intestine and caecum. The evenness was disturbed and the richness was decreased in the ERE groups. When the rabbits were suffering from ERE, the abundance of the Firmicutes was decreased in three parts of the digestive tract, whereas the Proteobacteria was increased in the stomach and caecum, the Bacteroidetes and Verrucomicrobia were increased in the small intestine. Correlation analysis showed that the reduced concentrations of TVFA and butyrate in the caeca of the ERE group were attributed to the decreased abundances of genera such as Lactobacillus, Alistipes and other fibrolytic bacteria and butyrate- producing bacteria such as Eubacterium and Faecalibacterium. It is concluded that, in terms of microorganisms, the overgrowth of Bacteroides fragilis, Clostridium perfringen, Enterobacter sakazakii and Akkermansia muciniphila and inhibition of Bifidobacterium spp. and Butyrivibrio fibrisolvens in the stomach, small intestine and caecum resulted in a decrease in butyrate yield, leading to the incidence of ERE, and the probability of developing ERE could be manipulated by adjusting the dietary fibre level.

Dietary supplements during the cold season increase rumen microbial abundance and improve rumen epithelium development in Tibetan sheep.

Livestock on the Qinghai-Tibetan Plateau are faced with extreme harsh winters and are often in negative energy balance during this period. Dietary supplementation can improve growth performance of Tibetan sheep and, consequently, we hypothesized that it would also increase microbial abundance and rumen epithelium development. To test this hypothesis, we examined the effect of feed supplementation during the cold season on rumen microbes, fermentation, epithelium development, and absorptive capability in Tibetan sheep. Eighteen 1-yr-old ewes (BW = 29.4 ± 1.79, kg) were offered oat hay ad libitum for 60 d and divided randomly into three groups: 1) no supplement; control group (CON); 2) urea-molasses lick block supplement (BS); and 3) concentrate feed supplement (CS). The ADG of CS ewes (143.3, g/d) was greater (P < 0.05) than BS ewes (87.9, g/d), which was greater (P < 0.05) than CON ewes (44.5, g/d). Serum concentrations of GH, IGF-1, and IGF-2 in the CS and BS groups were greater than in the CON group (P < 0.05). Greater relative abundance of protozoa, Ruminococcus albus, Fibrobacter succinogenes, Streptococcus bovis, and Ruminobacter amylophilus was observed in the CS and BS groups than in the CON group (P < 0.05), and relative abundances of rumen fungi, Butyrivibrio fibrisolvens, and Prevotella ruminicola in the CS group were greater than in the BS and CON groups (P < 0.05). Ruminal total VFA, ammonia, and microbial protein concentrations in the CS and BS groups were greater than in the CON group (P < 0.05), and in the CS group were greater than in the BS group (P < 0.05). Ruminal papillae width and surface area in the CS and BS groups were greater than in the CON group (P < 0.05), while in the CS group were greater than in the BS group (P < 0.05). The mRNA expressions of IGFBP5, NHE1 (sodium/hydrogen antiporter, isoform 1), DRA (downregulated in adenoma), and Na+/K+-ATPase (sodium/potassium ATPase pump) in ruminal epithelium were greater in the CS and BS groups than in the CON group (P < 0.05), and in the CS group was greater than in the BS group (P < 0.05), while NHE3 (sodium/hydrogen antiporter, isoform 3), MCT1 (monocarboxylate transporter 1), and MCT4 (monocarboxylate transporter 4) mRNA expressions in the CS group were greater than in the BS and CON groups (P < 0.05). It was concluded that supplementing Tibetan sheep during the cold season increases rumen microbial abundance and improves fermentation parameters, rumen epithelium development, and absorptive capability.

Efficacy and safety of chemotherapy or tyrosine kinase inhibitors combined with bevacizumab versus chemotherapy or tyrosine kinase inhibitors alone in the treatment of non-small cell lung cancer: a systematic review and meta-analysis.

The meta-analysis evaluated the efficacy and safety of chemotherapy or tyrosine kinase inhibitors combined with bevacizumab versus chemotherapy or tyrosine kinase inhibitors alone in the treatment of non-small cell lung cancer (NSCLC). The PubMed/MEDLINE, Ovid, Web of Science, CNKI, and the Cochrane Library database were searched for eligible randomized controlled trials comparing the combination of chemotherapy or epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) with bevacizumab to chemotherapy or EGFR-TKI alone. Main outcome measures were overall survival (OS), progression-free survival (PFS), objective response rate (ORR), and adverse effects. The pooled data were analyzed by STATA 12.0 and expressed as hazard ratio (HR) or risk ratio (RR), with their corresponding 95 % confidence intervals (95 % CI). Nine eligible trials comprising 3,547 patients (1,779 for bevacizumab and 1,768 for controls) were included in the study. Chemotherapy or TKIs in combination with bevacizumab significantly prolonged PFS (HRpfs 0.72, 95 % CIpfs 0.66-0.79, P pfs < 0.001) and OS (HRos 0.90, 95 % CIos 0.82-0.99, P os = 0.029) as first-line treatment for NSCLC compared with chemotherapy or TKIs alone. Bevacizumab combination regimens significantly prolonged PFS (HR 0.62, 95 % CI 0.52-0.74, P < 0.001) as second-line treatment; however, no benefit regarding OS was observed with the addition of bevacizumab (HR 0.94, 95 % CI 0.78-1.12, P = 0.479). The bevacizumab group showed increased ORR in both first- and second-line treatments. The high-dose bevacizumab subgroup in combination with chemotherapy showed a statistically significant improvement in OS, PFS, and ORR (HRos 0.89, 95 % CIos 0.80-0.99, P os 0.037; HRpfs 0.71, 95 % CIpfs 0.64-0.79, P pfs < 0.01, RRorr 1.85, 95 % CIorr 1.59-2.15, P orr < 0.001, respectively); however, the low-dose bevacizumab subgroup did not show enhanced OS (HRos 0.91, 95 % CIos 0.77-1.07, P os = 0.263), and a moderate improvement of PFS and ORR (HRpfs 0.85, 95 % CIpfs 0.72-1.00, P pfs = 0.049; RRorr 1.60, 95 % CIorr 1.28-2.0, P orr < 0.001). Erlotinib in combination with bevacizumab significantly prolonged PFS (HR 0.60, P < 0.001, 95 % CI 0.51-0.71) and increased ORR (RR 1.21, 95 % CI 0.98-1.49, P = 0.067) compared with erlotinib alone. A higher incidence of grade ≥3 adverse events such as proteinuria, hypertension, and hemorrhage was observed in the bevacizumab combination group than in the control group without bevacizumab (P all < 0.05). The addition of bevacizumab to chemotherapy or erlotinib can significantly improve PFS and ORR both in first- and second-line treatments of advanced NSCLC, with an acceptable risk of bleeding events, hypertension, proteinuria, and rash. Combination therapy with bevacizumab and chemotherapy is beneficial regarding OS; however, whether bevacizumab plus erlotinib can prolong OS need further validation.

Effects of different levels of protein supplementary diet on gene expressions related to intramuscular deposition in early-weaned yaks.

This study was conducted to estimate different levels of protein supplementary diet on gene expressions related to intramuscular deposition in early-weaned yaks. Results showed that supplementary dietary protein significantly increased final weight, average daily gain (ADG), intramuscular fat (IMF), serum free fatty acid (FFA), total triglycerides, total cholesterol (Ch), low-density lipoprotein cholesterol (LDL) and high-density lipoprotein cholesterol (HDL) content. There was a quadratic response of ADG, IMF, FFA, Ch, HDL and LDL to dietary crude protein (CP) level. Lipoprotein lipase (LPL), fatty acid synthase (FAS) and acetyl-CoA carboxylase (ACC) enzyme activities were significantly increased by supplementary dietary CP, while hormone-sensitive lipase (HSL) and carnitine palmitoyltransferase-1 (CPT-1) activities were significantly decreased. LPL, ACC and FAS enzyme activities showed quadratic increase as dietary CP increased. Peroxisome proliferator-activated receptor γ (PPARγ), LPL, FAS, sterol regulatory element binding protein 1 (SREBP-1), ACC, stearoyl-CoA desaturase (SCD) and heart fatty-acid binding protein (H-FABP) gene expression were significantly increased by supplementary dietary CP, while HSL and CPT-1 gene expression were significantly decreased. PPARγ, LPL, SREBP-1, ACC and H-FABP gene expression showed quadratic increase as dietary CP increased. These results indicated that supplementary dietary protein increased IMF accumulation mainly to increased intramuscular lipogenic gene expression and decreased lipolytic gene expression.

Concordant KRAS mutations in primary and metastatic colorectal cancer tissue specimens: a meta-analysis and systematic review.

A meta-analysis was performed to compare KRAS gene mutations in colorectal cancer tissue samples with primary and metastatic colorectal cancers. A total of 19 publications with 986 paired primary and distant metastases and 171 paired primary and lymph node metastases showed that KRAS genotype was highly concordant in primary and distant metastatic tumors, indicating that either type of tumor tissue could be useful as a source to detect KRAS mutations for selection of anti-EGFR therapy. However, lymph-node-metastatic tumors might not be suitable for diagnostic analysis of KRAS mutations due to an obvious discordant rate between primary and lymph-node-metastatic tumors.

Synergistic cytotoxic effects of recombinant human adenovirus p53 and radiation at various time points in A549 lung adenocarcinoma cells.

The aim of this study was to evaluate the effects of recombinant human adenovirus p53 (rAd-p53; Gendicine) transfection and radiation at various time points following transfection. Cytotoxic effects and p53 protein expression levels were analyzed. rAd-p53 containing the human wild-type p53 gene was introduced into the human lung adenocarcinoma cell line A549, and cells were irradiated with a single dose of 6 MeV 4 Gy ß rays. According to the time interval between rAd-p53 transfection and radiotherapy (RT), A549-transfected rAd-p53 cells were divided into 5 groups: radiation administered immediately after transfection (0 h-RT) group, after 3 h group (3 h-RT), after 6 h group (6 h-RT), after 24 h group (24 h-RT) and after 48 h group (48 h-RT). Cells with rAd-p53 transfection alone (Ad-p53) and with empty adenovirus (Ad) were included as the two control groups. Following 72 h of transfection, cell viability and growth were analyzed using MTT assays and flow cytometry, and p53 protein expression was analyzed using western blot analysis. From 0 h-RT to 48 h-RT, cell viability gradually decreased, while percentage of apoptotic cells and p53 protein expression gradually increased. The cell viability suppression rates in the 6 h-RT, 24 h-RT and 48 h-RT groups were 56.7±5.4, 60.8±6.0 and 68.9±6.6, respectively, which were significantly greater compared to that of the Ad-p53 (40.8±4.7), 0 h-RT (45.0±3.5) and 3 h-RT groups (47.0±4.3). No statistically significant differences were observed in the cell viability suppression rates among the 6 h-RT, 24 h-RT and 48 h-RT groups (P>0.05). Similar changes were observed in the percentage of apoptotic cells. The p53 protein expression level in the 6 h-RT group (0.856±0.092) was higher compared to that in the 3 h-RT group (0.643±0.089) (t=2.882; P=0.045), but not significantly different from that of the 24 h-RT group (1.193±0.202). The cell viability suppression rate and percentage of apoptotic cells was positively correlated with p53 protein expression in the A549 cells (P<0.05). Radiation may inhibit or damage p53 protein expression at the early stage of rAd-p53 transfection. To sensitize tumor cells to irradiation and achieve maximal cytotoxic effects, it is recommended to conduct RT at least 6 h following transfection with rAd-p53.

Altered expression of mitochondrial cytochrome c oxidase I and NADH dehydrogenase 4 transcripts associated with gastric tumorigenesis and tumor dedifferentiation.

This study aimed to detect the expression of mitochondrial mRNA in normal and cancerous gastric tissues and discuss their association with clinicopathological characteristics. Semi-quantitative reverse-transcription PCR was used to analyze mitochondrial transcripts in 42 cases of matched cancerous and normal gastric tissues. Expression of these genes was then statistically analyzed to determine the correlation with the clinicopathological characteristics from the patients. Transcripts of cytochrome c oxidase I (CO I) and NADH dehydrogenase 4 (ND4) were highly expressed in gastric cancer tissues compared to normal gastric tissues (P=0.005 and P=0.001, respectively). The expression levels of CO I and ND4 were higher in the diffused type of gastric cancer than in the intestinal type (P=0.024 and P=0.0002, respectively). Elevated expression of CO I and ND4 were associated with gastric tumorigenesis and tumor dedifferentiation ex vivo.

EGFR and KRAS mutations and altered c-Met gene copy numbers in primary non-small cell lung cancer and associated stage N2 lymph node-metastasis.

This study aimed to detect mutations in EGFR and KRAS and alterations of c-Met gene copy number (GCN) changes in primary and lymph node-metastatic NSCLCs. The data showed the concordant rate of EGFR genotype in primary and stage N2 lymph node-metastatic tumors was 95.45%. c-Met GCN in stage N2 lymph nodes was significantly higher than that of the primary tumors (P=0.038). The results suggest both primary and lymph-node metastases have relatively consistent EGFR mutations and EGFR mutations are not relevant to changes in c-Met GCN. c-Met GCN was increased significantly in EGFR TKI-naive patients with lymph node-metastatic tumors.

[Value of serum carcinoembryonic antigen in prediction of chemotherapy efficacy and prognosis in patients with advanced non-small cell lung cancer treated with EGFR-tyrosine kinase inhibitor].

OBJECTIVE: The aim of this study was to detect the pre- and post-treatment serum carcinoembryonic antigen (CEA) levels after 4 weeks of EGFR-TKIs treatment in advanced non-small cell lung cancer (NSCLC) patients to evaluate the clinical value of CEA in the prediction of chemotherapy response and prognosis in those patients. METHODS: Pre- and post-treatment serum CEA levels of the patients were measured with immunoradiometric kits after 4 weeks of EGFR-TKIs treatment to evaluate the relationship between chemotherapy response and prognosis. RESULTS: After 4 weeks of EGFR-TKIs treatment, one patient in the total of 75 patients (1.3%) achieved complete response (CR), 17 patients (22.7%) achieved partial response (PR), 31 patients (41.3%) achieved disease stable (SD) and 26 patients had progressive disease (PD). The radiological objective response rate(ORR) and disease control rate (DCR) were 24.0% and 65.3%, respectively. The median survival time (MST) of all patients was 8.1 months. The MST of SD patients was similar to that in the OR patients (P = 0.06), but both longer than that in the PD patients (P < 0.001). The MST of DC patients was similar to that in OR patients (P = 0.358), but longer than that in PD patients (P < 0.001). Serum CEA levels decreased ≥ 32% and ≥ 61% were closely related with the objective response and disease control. The median survival time (MST) of patients with serum CEA decreased ≥ 32% was longer than those with CEA decreased < 32% (9.5 months vs 6.7 months, P < 0.0001). The MST of patients with serum CEA decreased ≥ 32% was similar to those with CEA decreased ≥ 61% (9.5 months vs 10.5 months, P = 0.370), but both longer than those with CEA decreased < 32% (6.7 months, P < 0.001). Cox multivariate survival analysis confirmed that serum CEA level decreased ≥ 32%, CEA level decreased ≥ 61%, PS score, and DC are independent prognostic factor, but not OR. CONCLUSIONS: To advanced NSCLC patients, the disease control rate (DCR) may be more suitable than objective response rate (ORR) as an indicator in predicting the efficacy and prognosis in advanced NSCLC patients. Serum CEA levels decreased ≥ 32% may be a reliable indicator to determine the therapeutic efficacy of EGFR-TKIs.

Current evidences on XPC polymorphisms and breast cancer susceptibility: a meta-analysis.

Published data on the association between three polymorphisms (Lys939Gln, Ala499Val, and PAT±) of Xeroderma Pigmentosum group C (XPC) and breast cancer risk are inconclusive. To derive a more precise estimation of the relationship, a meta-analysis was performed. Crude ORs with 95% CIs were used to assess the strength of association between them. A total of 11 studies including 5,090 cases and 5,214 controls were involved in this meta-analysis. For XPC Lys939Gln polymorphism, no obvious associations were found for all genetic models when all studies were pooled into the meta-analysis (Lys/Gln vs. Lys/Lys: OR = 1.00, 95% CI 0.92-1.10; Gln/Gln vs. Lys/Lys: OR = 0.96, 95% CI 0.84-1.09; dominant model: OR = 0.99, 95% CI 0.91-1.08; and recessive model: OR = 0.97, 95% CI 0.86-1.09). In the subgroup analysis by ethnicity or study design, still no obvious associations were found. For XPC Ala499Val polymorphism, also no obvious associations were found for all genetic models when all studies were pooled into the meta-analysis (Val/Ala vs. Ala/Ala: OR = 0.91, 95% CI 0.79-1.05; Val/Val vs. Ala/Ala: OR = 1.07, 95% CI 0.80-1.44; dominant model: OR = 0.93, 95% CI 0.81-1.06; and recessive model: OR = 1.11, 95% CI 0.84-1.48). For XPC PAT± polymorphism, obvious associations were found for recessive model when all studies were pooled into the meta-analysis (OR = 1.41, 95% CI 1.05-1.89). In conclusion, this meta-analysis suggests that the XPC PAT± polymorphism allele may be a low-penetrant risk factor for developing breast cancer.

Identification of microRNA target genes in vivo.

MicroRNAs (miRNAs) are short non-coding RNAs transcribed from intergenic or intronic sequences as long precursors that are sequentially processed by the endonucleases Drosha and Dicer into short double-stranded sequences. It is clear that miRNAs play essential roles in gene expression, development, and cell fate specification in animals. However, one of the barriers of miRNA research is how to find the target genes. In this study, we have developed a rapid and effective method to isolate miRNA target genes in vivo. MicroRNA was synthesized in vitro and labeled by biotin. After transfected into cells, the miRNA/mRNA complexes were isolated by streptavidin-coated magnetic beads. hsa-miR155 was taken as model to validate this method, which is a very important modulator in tumor development. It is useful for validation of targets predicted in silico, and, potentially, for discovery of previously uncharacterized targets.