Peripheral blood T-cell receptor repertoire as a predictor of clinical outcomes in gastrointestinal cancer patients treated with PD-1 inhibitor.

BACKGROUND: Identifying valid biomarkers for patient selection impressively promotes the success of anti-PD-1 therapy. However, the unmet need for biomarkers in gastrointestinal (GI) cancers remains significant. We aimed to explore the predictive value of the circulating T-cell receptor (TCR) repertoire for clinical outcomes in GI cancers who received anti-PD-1 therapy. METHODS: 137 pre- and 79 post-treated peripheral blood samples were included. The TCR repertoire was evaluated by sequencing of complementarity-determining region 3 (CDR3) in the TRB gene. The Shannon index was used to measure the diversity of the TCR repertoire, and Morisita's overlap index was used to determine TCR repertoire similarities between pre- and post-treated samples. RESULTS: Among all enrolled patients, 76 received anti-PD-1 monotherapy and 61 received anti-PD-1 combination therapy. In the anti-PD-1 monotherapy cohort, patients with higher baseline TCR diversity exhibited a significantly higher disease control rate (77.8% vs. 47.2%; hazard ratio [HR] 3.92; 95% confidence interval [CI] 1.14-13.48; P = 0.030) and a longer progression-free survival (PFS) (median: 6.47 months vs. 2.77 months; HR 2.10; 95% CI 1.16-3.79; P = 0.014) and overall survival (OS) (median: NA vs. 8.97 months; HR 3.53; 95% CI 1.49-8.38; P = 0.004) than those with lower diversity. Moreover, patients with a higher TCR repertoire similarity still showed a superior PFS (4.43 months vs. 1.84 months; HR 13.98; 95% CI 4.37-44.68; P < 0.001) and OS (13.40 months vs. 6.12 months; HR 2.93; 95% CI 1.22-7.03; P = 0.016) even in the cohort with lower baseline diversity. However, neither biomarker showed predictive value in the anti-PD-1 combination therapy cohort. Interestingly, the combination of TCR diversity and PD-L1 expression can facilitate patient stratification in a pooled cohort. CONCLUSION: The circulating TCR repertoire can serve as a predictor of clinical outcomes in anti-PD-1 therapy in GI cancers.

The impact of surgical margin status on prostate cancer-specific mortality after radical prostatectomy: a systematic review and meta-analysis.

BACKGROUND: Until now, there is no clear conclusion on the relationship between the surgical margin status after radical prostatectomy (RP) and prostate cancer-specific mortality (PCSM). Therefore, we conducted this systematic review and meta-analysis based on all eligible case-control studies. METHODS: A systematic and comprehensive literature search was performed based on PUBMED and EMBASE to identify all of the potentially relevant publications which were published before September 2019. Hazard ratio (HR) for PCSM was independently extracted by two reviewers from all eligible studies. Pooled HR estimates with their corresponding 95% confidence intervals (95% CIs) were computed by Stata12.0. RESULTS: Total 15 eligible studies were included in this meta-analysis. The pooled results showed that patients with positive surgical margin (PSM) after RP may have higher PCSM than those who had a negative surgical margin (HR 1.44, P = 0.043). In the subgroup analysis, we found that no matter whether the pathological stage of the patients is T2 or T3, PSM is indicative of a high PCSM and that the PCSM of T3 is higher than T2 (Pathological stage T3, HR 1.77, P = 0.032; Pathological stage T2, HR 1.56, P = 0.003). In addition, by performing the subgroup analysis of Gleason score, we concluded that both Gleason score 8-10 and Gleason score ≤ 7 would increase the risk of PCSM, and the former was more significant than the latter (Gleason score 8-10, HR 1.88, P < 0.001; Gleason score ≤ 7, HR 1.38, P = 0.039). Moreover, PSM increased PCSM regardless of whether the patients received radiation therapy or not (radiation therapy, HR 1.92, P < 0.001; no radiation therapy, HR 1.42, P < 0.001). CONCLUSIONS: This meta-analysis demonstrated that patients with PSM after RP may have an elevated PCSM. However, to evaluate these correlations in more details, it is necessary to conduct further studies on a larger sample size.

Dynamic monitoring of HER2 amplification in circulating DNA of patients with metastatic colorectal cancer treated with cetuximab.

PURPOSE: Cetuximab (CTX) has been used to treat metastatic colorectal cancer (mCRC) with wild-type (wt) RAS and BRAF genes. Meanwhile HER2 amplification reportedly denoted CTX-resistant mCRC tumors. We investigated whether monitoring of HER2 amplification in circulating DNA allowed early detection of mCRC progression and CTX resistance. METHODS: We analyzed HER2 amplification in circulating DNA at 8-week intervals using ddPCR from 36 patients with RASwt/BRAFwt mCRC, who progressed after CTX treatments between July 2015 and January 2018. RESULTS: Of the 36 patients, 5 (13.9%) exhibited dynamic fluctuations of HER2 amplification in plasma in the course of CTX treatment, of whom 2 were positive for HER2 amplification in matched tumor specimens at baseline (per FISH). All 5 primary sites were left side: 3 rectums and 2 descending colon. HER2 ratio fluctuations in circulating DNA not only reflected changes in tumor volume, but their obvious increases presaged CT-documented progress by an average lead time of 2 months. Interestingly, progression-free survival did not significantly differ between these 5 patients and those without HER2 amplification (HR 1.06, 95% CI 0.40-2.77, P = 0.909). CONCLUSION: Plasma HER2 amplification detected by ddPCR changed over time and predicted resistance to CTX, by an average lead time of 2 months. Further study is needed to validate our findings.

The impact of PTEN deletion and ERG rearrangement on recurrence after treatment for prostate cancer: a systematic review and meta-analysis.

BACKGROUND: The specific association between PTEN deletion or ERG rearrangement and the recurrence of prostate cancer (PC) treated with radical prostatectomy (RP) or brachytherapy is still unelaborated. Therefore, we performed a comprehensive meta­analysis to understand the impact of these factors on cancer recurrence. METHODS: A comprehensive literature search was performed in November 2018 based on PUBMED, EMBASE and Web of science database. Hazard ratio (HR) for biochemical recurrence free (BRF) which was defined as a PSA greater than or equal to 0.4 ng/mL after RP or another therapy for any detectable PSA and recurrence-free survival (RFS) which defined the time from the beginning of treatment to the earliest occurrence of local recurrence, distant metastasis or death. Which were extracted from eligible studies. I2 value was used to assess the pooled heterogeneity. RESULT: A total of 6744 patients from 17 studies were included in this analysis Overall, The pooled results showed that PTEN loss predict pooled BRF (HR 1.79, 95% CI 1.49-2.16, P < 0.001) and RFS (HR 1.71, 95% CI 1.50-1.95, P < 0.001) in patients after radical prostatectomy or brachytherapy for prostate cancer. Subgroup analysis revealed that PTEN deletion significantly predicted poor BRF or RFS in heterozygous studies group (HR 1.70, 95% CI 1.31-2.21, P < 0.001). The PTEN deletion also significantly predicted poor BRF or PFS in homozygous studies (HR 2.54, 95% CI 1.89-3.17, P < 0.001). And we had found that there was no significant association between ERG rearrangement and cancer recurrence regardless of PTEN loss or not. In addition, we concluded that Gleason score > 6 significantly predicted the poor BRF or RFS in studies, especially in Gleason score = 4 + 3 (HR 3.16, 95% CI 2.08-4.80, P < 0.01). CONCLUSION: This study presented that PTEN deletion significantly reduce time of BRF or RFS, especially based on homozygous deletion. And we also found ERG rearrangement in tumor cell could not significantly predict BRF or RFS.

The incidence proportion of erectile dysfunction in patients treated with cryotherapy for prostate cancer: a meta-analysis.

OBJECTIVES: With the maturity of cryotherapy for prostate cancer, the complications after operation are also decreasing, which can improve the prognosis of patients. However, erectile dysfunction (ED) is still one of the main complications after cryotherapy. Therefore, we performed a meta-analysis to evaluate the incidence of erectile dysfunction in patients after cryotherapy. MATERIALS AND METHODS: A comprehensive literature search was performed in August 2018. PUBMED and EMBASE databases were searched to collect studies reporting the incidence rate of ED after cryotherapy from 2002 to 2018. Two reviewers independently screened the literatures, extracted data and assessed the risk of bias of included studies. Pooled ratio and its 95% confidence intervals (95% CIs) were performed by Stata 12.1. RESULTS: Of the 157 articles identified on August 1st 2018, 23 studies which reported ED after cold ablative therapy were identified, however, only 12 used validated outcome measures and met inclusion criteria. A total of 12 studies were included in this meta-analysis. Overall, the results of this meta-analysis showed that the pooled incidence rate of ED was 0.27 (95% CI 0.26-0.28) which means that the incidence rate of ED after cryotherapy for prostate cancer was not high, but we still found that there are great heterogeneity between the 12 articles. By subgroup analysis, we found a statistically significant incidence rate of ED in primarily localized PCa which was 0.49 (95% CI 0.30-0.68), which is clearly lower than the incidence of recurrent prostate cancer after failed primary radiotherapy 0.61 (95% CI 0.43-0.79). CONCLUSION: ED is one of the major complications after cryotherapy for PCa. Furthermore, subgroup analysis revealed a higher incidence rate in PCa undergoing radiotherapy. Significantly, with the development of cryotherapy technology, the incidence of ED after cryotherapy for prostate cancer is decreasing. While we still need further researches to advance knowledge in this field.

Identification a novel set of 6 differential expressed genes in prostate cancer that can potentially predict biochemical recurrence after curative surgery.

PURPOSE: Approximately, 30% patients after radical prostatectomy (RP) will undergo post-operative biochemical recurrence (BCR). Present stratification method by TNM staging and Gleason score was not adequate to screen high-risk patients. In this study, we intended to identify a novel set of differentially expressed gene (DEG) signature that can predict BCR after RP. MATERIALS/PATIENTS: 358 patients after RP with follow-up data were extracted from The Cancer Genome Atlas (TCGA), among which 61 patients had undergone BCR. Key DEGs were confirmed by the intersection of GSE35988 and TCGA_PCa dataset, and their gene expression data were also extracted from TCGA_PCa dataset. Kaplan-Meier plot and Cox proportion hazard regression model were applied to assess the relationship between risk score and survival outcome (BCR). RESULTS: 310 DEGs were confirmed in two prostate cancer dataset. 6 DEGs (SMIM22, NINL, NRG2, TOP2A, REPS2, and TPCN2) were selected to construct a risk score formula. The risk score was a powerful predictive factor independent of TNM stage (HR 3.045, 95% CI 1.655-5.602, p < 0.001). CONCLUSION: In this study, a novel 6-gene signature with robust predictive ability on post-operative BCR was constructed and 4 genes (SMIM22, NRG2, NINL and TPCN2) in the 6-gene signature were not reported to be associated with prostate cancer.

Citron kinase (CIT-K) promotes aggressiveness and tumorigenesis of breast cancer cells in vitro and in vivo: preliminary study of the underlying mechanism.

OBJECTIVES: Citron kinase (CIT-K), as a key Rho effector, functions to maintain proper structure of the midbody during cell mitosis. This study assessed CIT-K expression and its role in breast cancer cells. METHODS: Paraffin-embedded breast cancer and para-tumor tissues from 43 invasive breast cancer patients and 33 normal mammary glands were collected for immunohistochemistry. CIT-K expression knockdown was achieved using lentivirus carrying CIT-K shRNA in a wide range of breast cancer cell lines. Cells were then subjected to Western blot, qRT-PCR, cell proliferation, colony formation, transwell, and flow cytometric assays. The tumorigenicity of CIT-K knocked-down breast cancer cells was assessed using the nude mouse xenograft assay. Microarray analysis was performed to elucidate the underlying gene regulation after CIT-K silencing. RESULTS: CIT-K protein was overexpressed in breast cancer tissues, which is associated with advanced tumor stage, HER-2 expression and Ki-67 expression, whereas knockdown of CIT-K expression reduced breast cancer cell proliferation and colony formation, but promoted tumor cell apoptosis and cell-cycle arrest. Knockdown of CIT-K expression also inhibited breast cancer cell migration and invasion capacity. Moreover, CIT-K knockdown suppressed the tumorigenicity of breast cancer cells in nude mice. Molecularly, the expression of a variety of signaling genes, such as cyclin D1, EGFR, JAK1, TGF-α, PTK2, RAF1, RALB, SOS1, mTOR, and PTGS2, were altered after CIT-K knockdown. CONCLUSIONS: This study demonstrated that CIT-K is associated with aggressive breast cancer behavior and targeting CIT-K may be a novel strategy for the future control of breast cancer.

Traditional medicines used by Q'eqchi' Maya to treat diabetic symptoms and their antiglycation potential.

ETHNOPHARMACOLOGICAL RELEVANCE: Because of the recent increase in type 2 diabetes and the need for complementary treatments in remote communities in many parts of the world, we undertook a study of treatments for diabetic symptoms used by traditional Q'eqchi' Maya healers of Belize. We used quantitative ethnobotany to rank culturally important taxa and subsequent pharmacological and phytochemical studies to assess bioactivity. MATERIALS AND METHODS: Antidiabetic plants identified in field interviews with traditional healers were ranked by syndromic importance value (SIV) based on 15 symptoms of diabetes. Species ranked with high SIV were tested in an assay relevant to many diabetes complications, the advanced glycation endproduct (AGE) inhibition assay. Active principles were identified by phytochemical analysis and bioassay. RESULTS: We collected over 70 plant species having a promising SIV score. The plants represented a broad range of neotropical taxa. Selected Q'eqchi' antidiabetic plants with high SIV were collected in bulk and tested in the advanced glycation endproduct (AGE) inhibition assay. All plant extracts showed AGE inhibition and the half maximal inhibitory concentration (IC50) ranged from 40.8 to 733 µg/mL, while the most active species was Tynanthus guatemalensis Donn (Bignoniaceae). A linear regression showed a significant relationship between 1/ IC50 and SIV. Phytochemical analysis revealed the presence of verbascoside, as a major component and active principle of the T guatemalensis which had an IC50 = 5.1 µg/mL, comparable to the positive control quercetin. CONCLUSION: The results reveal a rich botanical tradition of antidiabetic symptom treatments among the Q'eqchi'. Study of highly ranked plants revealed their activity in AGE inhibition correlated with SIV. T. guatemalensis was identified as a promising species for further evaluation and local use.

Application of EGFR inhibitor reduces circulating tumor cells during transcatheter arterial embolization.

PURPOSE: Transcatheter arterial embolization (TAE) has been widely used in treating non-curative hepatocellular carcinoma (HCC). However, it is noticed that TAE may cause invasion of some cancer cells into circulation, resulting in distal metastasis and poor therapeutic outcome. Here, we aimed to reduce the side effects of TAE using the inhibitors for epidermal growth factor receptor (EGFR). METHODS: Transient hepatic artery ligation (HAL) was used as a mouse model for TAE. EGFR inhibitors were applied. Tumor size, presence of tumor cells in circulation, distal tumor formation, and activation of genes associated with tumor cell invasion and metastasis were analyzed. RESULTS: Inhibitors for EGFR significantly reduced the size of primary tumor, presence of tumor cells in circulation, and distal tumor formation after HAL. Further studies showed that EGFR inhibition suppressed several genes associated with tumor cell invasion and metastasis, such as vascular endothelial growth factor-A, stromal cell-derived factor 1, and Slug. CONCLUSION: EGFR inhibitor application may reduce circulating cancer cells during TAE and thus improve the therapy for advanced HCC.

Differential gene expression in the peripheral blood of Chinese Sanhe cattle exposed to severe cold stress.

Livestock is an important food resource for the inhabitants of cold regions, such as northern Asia and alpine regions, where agriculture is limited. In these regions, cold stress largely affects livestock production, thereby reducing the productivity and survival of animals. Despite the importance of breeding cold-tolerant animals, few studies have investigated the effects of cold stress on cattle. Furthermore, whether severe cold stress alters gene expression or affects molecular genetic mechanisms remains unknown. Thus, we investigated gene expression changes in the peripheral blood samples of the Chinese Sanhe cattle exposed to severe cold. A total of 193 genes were found to exhibit significant alteration in expression (P < 0.05; fold change > 1.3), with 107 genes showing upregulation and 86 showing downregulation after cold exposure. The differences in the expression of 10 selected genes were further validated by real-time qRT-PCR. Further analyses showed that these differentially expressed genes (DEGs) were predominantly associated with important biological pathways and gene networks, such as lipid metabolism and cell death and survival, which are potentially associated with severe cold-stress resistance. Identification and description of these cold stress-induced DEGs might lead to the discovery of novel blood biomarkers that could be used to assess cold-stress resistance in cattle. To our knowledge, this is the first genomic evidence of differences in the transcript expression pattern in cattle exposed to severe cold stress. Our findings provide insights on the potential molecular mechanisms underlying cold-stress response in cattle.

Primary cultures of mouse small intestinal epithelial cells using the dissociating enzyme type I collagenase and hyaluronidase.

The epithelium is a highly dynamic system, which plays a crucial role in the homeostasis of the intestinal tract. However, studies on the physiological and pathophysiological functions of intestinal epithelial cells (IECs) have been hampered due to lack of normal epithelial cell models. In the present study, we established a reproducible method for primary culture of mouse IECs, which were isolated from the viable small intestinal crypts of murine fetuses (on embryonic day 19), using type I collagenase and hyaluronidase in a short span of time (≤20 min). With this method, continuously growing mouse IECs, which can be subcultured over a number of passages, were obtained. The obtained cell lines formed a tight cobblestone-like arrangement, displayed long and slender microvilli, expressed characteristic markers (cytokeratin 18 and Notch-1), and generated increasing transepithelial electrical resistance and low paracellular permeability during in vitro culture. The cells also had enzymatic activities of alkaline phosphatase and sucrase-isomaltase, and secreted various cytokines (IL-1ß, IL-6, IL-8, and monocyte chemoattractant protein-1), responding to the stimulation of Escherichia coli. These results show that the primary-cultured mouse IECs obtained by the method established here had the morphological and immunological characteristics of IECs. This culture system can be a beneficial in vitro model for studies on mucosal immunology and toxicology.

Translocation breakpoints of chromosome 4 in male carriers: clinical features and implications for genetic counseling.

Cytogenetic analysis remains a powerful and cost-effective technology, and has wide applicability in genetic counseling for infertile males. Chromosomal rearrangements are thought to be one of the major genetic factors that influence male infertility. Some carriers with balanced reciprocal translocation have been identified as having oligozoospermia or azoospermia, and there is an association between balanced translocation and recurrent abortion. Researchers have reported the involvement of chromosome 4 translocations in male factor infertility and recurrent miscarriages. A translocation breakpoint might interrupt the structure of an important gene, and it is associated with reproductive failure. However, the clinical characteristics of the breakpoints in chromosome 4 translocations have not been studied. Here, we report the breakpoints in chromosome 4 translocation and the clinical features presented in carriers to enable informed genetic counseling of these patients. Of 82 patients with balanced reciprocal translocations, 14 were carriers of the chromosome 4 translocation: four presented with pregestational infertility (clinical manifestations: oligozoospermia, severe oligozoospermia, or azoospermia), whereas 10 presented with gestational infertility (able to conceive but with a tendency to miscarry). The breakpoint at 4q12 was associated with pregestational infertility, whereas the breakpoints at 4q13, 4q21, 4q25, and 4q32 were associated with gestational infertility. However, the breakpoint at 4q35 was associated with both pregestational and gestational infertility. Chromosome 4 translocation carriers with pregestational or gestational infertility should be counseled on chromosomal breakpoints and the different technologies available to assist reproduction.

Chromosome 7 translocation breakpoints in male carriers: clinical features and implications for genetic counseling.

Balanced reciprocal translocations are associated with reproductive failure. Some reciprocal translocation carriers exhibit azoospermia or oligozoospermia, and an association exists between these chromosomal abnormalities and recurrent abortion. Previous reports have indicated the involvement of chromosome 7 translocations in male infertility and recurrent miscarriage. A translocation breakpoint can occur within an important gene, interrupting its structure and leading to male infertility. However, clinical characteristics resulting from chromosome 7 translocation breakpoints have not been studied. Here, we report such breakpoints and their associated clinical features, to enable informed genetic counseling of carriers. Balanced reciprocal translocations were found in 1.57% of the tested patients. Among these 82 individuals, 14 (17.07%) carried a chromosome 7 translocation, of which, five presented with pregestational infertility and clinical manifestations of oligozoospermia or necrospermia, while nine presented with gestational infertility (i.e., were able to conceive, but often resulting in miscarriage). Breakpoints at 7q31 and 7q36 were associated with pregestational infertility, whereas those at 7p10, 7q21.2, 7q22, and 7q32 were connected to gestational infertility. However, the breakpoint at 7p15 was associated with both. Chromosome 7 translocation carriers with pregestational or gestational infertility should be counseled on chromosomal breakpoints and the various molecular technologies available for assisted reproduction.

Translocation breakpoints of chromosome 1 in male carriers: clinical features and implications for genetic counseling.

Reciprocal translocation is closely associated with male infertility and recurrent miscarriages. Balanced reciprocal translocations associated with reproductive failures are predominantly observed on chromosome 1. Additionally, infertile male patients present a number of breakpoints throughout chromosome 1. A translocation breakpoint might interrupt the structure of an important gene, leading to male infertility. Here, we report the breakpoints on chromosome 1 translocation and the clinical features presented in carriers, to enable informed genetic counseling of these patients. Balanced reciprocal translocations were found in 1.57% of the tested patients. Among 82 patients, 23 patients (28.05%) were carriers of the chromosome 1 translocation: 12 presented pre-gestational infertility with clinical manifestations of azoospermia or oligozoospermia, while 11 patients presented gestational infertility (able to conceive but with a tendency to miscarry or give birth to a stillborn). The breakpoint at 1p22 was predominantly observed in these patients; additionally, breakpoints at 1p31.2, 1p10, and 1q25 were associated with gestational infertility. Breakpoints at 1p13, 1q12, and 1q21 were associated with pre-gestational infertility. These results suggested that breakpoints at 1p32, 1p13, and 1q21 were predominantly associated with pre-gestational infertility, while that at 1q25 was associated with gestational infertility. Chromosome 1 translocation carriers with infertility presenting as azoospermia or oligospermia should be counseled on chromosomal breakpoints and the different molecular technologies available to facilitate reproduction.

Balanced reciprocal translocation at amniocentesis: cytogenetic detection and implications for genetic counseling.

Balanced translocation is a common structural chromosomal rearrangement in humans. Carriers can be phenotypically normal but have an increased risk of pregnancy loss, fetal death, and the transmission of chromosomal abnormalities to their offspring. Existing prenatal screening technologies and diagnostic procedures fail to detect balanced translocation, so genetic counseling for carriers remains a challenge. Here, we report the characteristics of chromosomal reciprocal translocation in 3807 amniocentesis cases. Of the 16 detected cases of fetal reciprocal translocation, 8 cases (50%) showed positive biochemical marker screening; 3 cases (18.75%) were the parental carriers of a chromosomal abnormality; 2 (12.5%) were of advanced maternal age, 2 (12.5%) had a previous history of children with genetic disorders, and 1 case (6.25%) was associated with positive soft markers in obstetric ultrasound. Chromosomes 5 and 19 were the most commonly involved chromosomes in balanced translocations. Of the 13 cases with fetal balanced translocations, 8 (61.5%) were inherited from a paternal chromosome, 3 (23.1%) from a maternal chromosome, and 2 (15.4%) cases were de novo. The incidence of balanced translocation at amniocentesis was 0.42%. Male carriers of reciprocal chromosome translocation appear to have a higher chance of becoming a parent of a child born by normal childbirth than female carriers.

Increased miR-155-5p expression in dermal mesenchymal stem cells of psoriatic patients: comparing the microRNA expression profile by microarray.

Mesenchymal stem cells (MSCs) have pleiotropic immuno-modulatory effects and pro-angiogenic ability, leading to the presumption that MSCs may be involved in the pathogenesis of many inflammatory or autoimmune disorders, including psoriasis. In a previous study, we reported the specific gene expression profile of dermal MSCs from psoriasis. Inflammation- and angiogenesis-related genes, such as lipopolysaccharide-induced tumor necrosis factor-alpha transcription factor (LITAF), dual-specificity protein phosphatase 1 (DUSP1), vascular endothelial growth factor α (VEGFα), and insulin-like growth factor-binding protein-5 (IGFBP5), are abnormally expressed in psoriatic dermal MSCs. As a key regulator of gene expression, miRNA are involved in a wide variety of biological processes; in fact, several miRNAs have been implicated in the development and progression of inflammatory or autoimmune disorders. In this study, we compared the miRNA expression profiles of dermal MSCs from patients with psoriasis to those in MSCs from normal individuals by microarray, and found that the pro-inflammatory miRNA miR-155 was significantly overexpressed in psoriatic MSCs (2.44 fold, P < 0.001). Additionally, the expression of miR-155 target gene TAB2 (8.47 ± 1.55 vs 6.38 ± 2.10, P < 0.01,) and the downstream gene iNOS (5.26 ± 2.58 vs 3.73 ± 1.89, P < 0.05) was found to be inhibited in psoriatic dermal MSCs by real-time PCR. Therefore, we speculated that the elevation in miR-155 levels may be an indicator of, or a key regulatory pathway in, the pathogenesis of psoriasis, resulting in functionally impaired dermal MSCs.

A computational method to predict carbonylation sites in yeast proteins.

Several post-translational modifications (PTM) have been discussed in literature. Among a variety of oxidative stress-induced PTM, protein carbonylation is considered a biomarker of oxidative stress. Only certain proteins can be carbonylated because only four amino acid residues, namely lysine (K), arginine (R), threonine (T) and proline (P), are susceptible to carbonylation. The yeast proteome is an excellent model to explore oxidative stress, especially protein carbonylation. Current experimental approaches in identifying carbonylation sites are expensive, time-consuming and limited in their abilities to process proteins. Furthermore, there is no bioinformational method to predict carbonylation sites in yeast proteins. Therefore, we propose a computational method to predict yeast carbonylation sites. This method has total accuracies of 86.32, 85.89, 84.80, and 86.80% in predicting the carbonylation sites of K, R, T, and P, respectively. These results were confirmed by 10-fold cross-validation. The ability to identify carbonylation sites in different kinds of features was analyzed and the position-specific composition of the modification site-flanking residues was discussed. Additionally, a software tool has been developed to help with the calculations in this method. Datasets and the software are available at https://sourceforge.net/projects/hqlstudio/ files/CarSpred.Y/.

De novo interstitial deletion in the long arm of chromosome 11: a case report.

The 11q terminal deletion disorder is a rare genetic disorder associated with numerous clinical features. A few case reports have been made about de novo interstitial deletion of chromosome 11q. However, due to the heterogeneity in size and position of the deletions, a clear genotype-phenotype correlation is not easily made. Here we report a case interstitial 20.5-Mb deletion at chromosome 11q13.4q21, as confirmed by array comparative genomic hybridization. Dysmorphic features such as coarse facial features, congenital laryngomalacia, oblique inguinal hernia, high-arched palate, and camptodactyly were observed in the subject. The present case broadens the spectrum of clinical findings observed in individuals with 11q interstitial deletion.

Correlation between IL-3 and IL-13 gene polymorphisms in Chinese patients and rheumatoid arthritis.

The aim of this study was to examine the association between polymorphisms in the interleukin-3 and -13 (IL-3 and IL-13) genes and rheumatoid arthritis (RA). In this hospital-based case-control study, we analyzed the IL-3 rs2073506 G/A, IL-3 rs40401 C/T, and IL-13 rs1800925 C/T polymorphisms in 615 RA patients and 839 controls from a Chinese Han population. Genotyping was performed using a custom-by-design 48-Plex single nucleotide polymorphism scanTM kit. Our results indicated that the IL-3 rs2073506 G/A, IL-3 rs40401 C/T, and IL-13 rs1800925 C/T polymorphisms were not associated with RA. However, stratification analyses suggested that the IL-13 rs1800925 CT and CT/CC genotypes increased the risk of RA in patients with erythrocyte sedimentation rate (ESR) <25.00. To sum up, these findings suggest that the IL-13 rs1800925 C/T polymorphism may be associated with increased risk of RA in ESR <25.00 patients. Future studies with larger sample sizes and inclusion of other ethnic populations must be conducted to confirm the findings of this study.

Patients with brain metastases derived from gastrointestinal cancer: clinical characteristics and prognostic factors.

PURPOSE: This study seeks to evaluate the natural history, outcome, and possible prognostic factors in patients with brain metastases derived from gastrointestinal cancers. METHODS: The clinical features, prognostic factors, and the effects of different treatment modalities on survival were retrospectively investigated in 103 patients with brain metastases derived from gastrointestinal cancers. RESULTS: The median time from diagnosis of primary tumor to brain metastasis was 22.00 months. The interval between diagnosis of primary tumor relapse and brain metastasis was 8.00 months. The median follow-up time was 7.80 months. The median survival time after diagnosis of brain metastases was 4.10 months for all patients and 1.17 months for patients who received only steroids (36.9 %), 3.97 months for patients who only received whole-brain radiation therapy (WBRT 31.1 %), 11.07 months for patients who received gamma-knife surgery alone or/and WBRT (20.4 %), and 13.70 months for patients who underwent surgery and radiotherapy (12 patients, 11.6 %) (P < 0.001). Multivariate analysis revealed that recursive partitioning analysis (RPA) class, extracranial metastasis, and chemotherapy were independent prognostic factors. Brain metastasis derived from gastrointestinal tract cancer is rare, and overall patient survival is poor. CONCLUSION: RPA class, chemotherapy after brain metastases, and treatment regimens were independent prognostic factors for the survival of patients with brain metastases derived from gastrointestinal cancers.