Plasma THBS1 as a predictive biomarker for poor prognosis and brain metastasis in patients with HER2-enriched breast cancer.

BACKGROUND: Thrombospondin-1 (THBS1) is a secretory adhesive glycoprotein involved in the progression of multiple malignancies, including breast cancer. However, the clinical significance and prognostic role of plasma THBS1 in breast cancer have yet to be clarified. METHODS: Plasma THBS1 levels in 627 breast cancer patients were analyzed by enzyme-linked immunosorbent assay. Bone marrow blood was drawn from the anterior/posterior superior iliac spine to detect the presence of disseminated tumor cells (DTCs). The effects of plasma THBS1 on the clinicopathological characteristics and survival prediction of breast cancer patients were explored. RESULTS: Plasma THBS1 did not correlate with overall survival, breast cancer-specific survival (BCSS), and distant disease-free survival (DDFS) in the entire breast cancer cohort. Notably, HER2-enriched patients with high-plasma THBS1 levels had significantly shorter BCSS (P = 0.027) and DDFS (P = 0.011) than those with low levels. Multivariate analyses revealed that plasma THBS1 was an independent prognostic marker of BCSS (P = 0.026) and DDFS (P = 0.007) in HER2-enriched patients. THBS1 levels were 24% higher in positive DTC patients than in negative DTC patients (P = 0.031), and high levels were significantly associated with poor BCSS in positive DTC patients (HR 2.08, 95% CI 1.17-3.71; P = 0.019). Moreover, high-plasma THBS1 levels were specifically associated with an increased occurrence of brain metastasis in HER2-enriched patients (P = 0.041). CONCLUSION: These findings suggest that plasma THBS1 may be serving as an unfavorable prognosis predictor for HER2-enriched breast cancer and justifies the need for further research.

Preliminary exploration of the effects of environmental factors on the microsatellite status of BRAF-mutated colorectal cancer.

BACKGROUND: To investigate the expression of EBV products and frequency of gallstone disease (GD) among different microsatellite status in colorectal cancer (CRC) with BRAFV600E mutation. METHODS: We collected 30 CRC patients with BRAFV600E mutation and 10 BRAF ( -) CRC patients as well as 54 healthy subjects. Tumor tissue samples were collected to detect the mutation of BRAF, KRAS, and TP53. Microsatellite status was determined by immunohistochemistry and PCR. EBER in situ hybridization was performed to detect EBV. In addition, we also collected clinical information about the patients. RESULTS: We found that although EBV products were detected in CRC, there were no significant differences in the EBV distribution between the different BRAF groups. Our study demonstrated that BRAFV600E mutation and BRAFV600E with MSI were significantly more frequent in the right CRC. Furthermore, the KRAS mutation rate in the BRAF-wild-type group was proved to be significantly higher than that in the BRAF mutation group. In addition, we revealed that BRAF mutation and MSI were independent risk factors of TNM stage. The frequency of GD was higher in CRC patients than in general population, and although there was no significant difference between CRC with or without BRAFV600E mutation, the highest frequency of GD was found in MSS CRC with BRAFV600E mutation. CONCLUSIONS: EBV plays a role in CRC, but is not a determinant of different microsatellite status in CRC with BRAFV600E mutation. The frequency of GD in MSS CRC with BRAFV600E mutation is significantly higher than that in the general population.

Erratum: High-background parenchymal enhancement in the contralateral breast is an imaging biomarker for favorable prognosis in patients with triple-negative breast cancer treated with chemotherapy.

[This corrects the article on p. 4422 in vol. 13, PMID: 34150024.].

Pregnancy-induced changes to the gut microbiota drive macrophage pyroptosis and exacerbate septic inflammation.

The physiological and immune changes that occur during pregnancy are associated with worsened disease outcomes during infection and sepsis. How these perturbations exacerbate inflammation has not been explored. Here, using antibiotic treatment and fecal microbial transfers, we showed that sepsis susceptibility is driven by pregnancy-induced changes to gut microbiome in mice and humans. Integrative multiomics and genetically engineered bacteria revealed that reduced Parabacteroides merdae (P. merdae) abundance during pregnancy led to decreased formononetin (FMN) and increased macrophage death. Mechanistically, FMN inhibited macrophage pyroptosis by suppressing nuclear accumulation of hnRNPUL2 and subsequent binding to the Nlrp3 promoter. Treatment with FMN or deletion of murine hnRNPUL2 protected against septic inflammation. Intestinal abundances of P. merdae and FMN inversely correlated with the progression of septic patients. Our data reveal a microbe-immune axis that is disrupted in pregnant septic hosts, highlighting the potential of the FMN-hnRNPUL2-NLRP3 axis in providing promising therapeutic strategies for sepsis.

Molecular subtypes predict the prognosis of male breast cancer: a retrospective cohort study.

Background: Male breast cancer is rare, and something different from female breast cancer. The characteristics of molecular subtype in male breast cancer is unclear and lack of large-sample study. Methods: A retrospective study was conducted to investigate the characteristics and prognosis of patients with male breast cancer using the data recorded in the Surveillance, Epidemiology, and End Results (SEER) database from 2010-2014. A total of 1,597 cases were enrolled with median age of 66 years. The study endpoint was considered as patient death. The molecular subtype was defined by estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER2) status, hormone receptor (HR) positive was defined as ER positive with or without PR positive, including 1,373 cases of HR+/HER2- tumor (86%), 182 cases of HR+/HER2+ tumor (11.4%), 13 cases of HR-/HER2+ tumor (0.8%) and 29 cases with triple negative (TN) tumor (1.8%), respectively. Results: There were significant differences in distributions of age, race, grade, tumor size and American Joint Committee on Cancer (AJCC) stage between different molecular subtypes. Patients of different molecular subtypes differed significantly in 5 years overall survival and cause-specific survival (CSS). Five-year CSS (5y-CSS) rates of different molecular subtypes was 89.2% (HER2-/HR+), 78.4% (HER2+/HR+), 72.6% (HER2+/HR-) and 43.2% (TN), respectively. According to Cox regression, age ≥65 years [P=0.001, hazard ratio (HR) =2.136 (1.372, 3.324)], ER negative [P=0.02, HR =2.481 (1.159, 5.319)], PR negative [P=0.007, HR =2.294 (1.256, 4.184)], TN subtype [P<0.001, HR =10.676 (4.441, 25.665)], AJCC stage IV [P<0.001, HR =21.222 (10.377, 43.4)], tumor size >5 cm or T4 [P<0.001, HR =2.577 (0.978, 6.792)], Stage M1 [P=0.001, HR =4.519 (1.929, 10.587)] and Black race [P=0.002, HR =2.322 (1.442, 3.74)] were independent prognostic factors for poorer CSS. Conclusions: Just like female, molecular subtypes also varied in male breast cancer. It could be a predictor for survival and improve the strategy making in clinical practice.

Downregulation of ZNF280A inhibits proliferation and tumorigenicity of colorectal cancer cells by promoting the ubiquitination and degradation of RPS14.

Colorectal cancer (CRC), one of the cancers with highest mortality, involves complicated molecular mechanisms leading to the onset of malignant phenotypes. ZNF280A, a member of the zinc-finger protein family, was shown to be a promotor of oncogenesis in CRC in this study. ZNF280A was remarkably upregulated in CRC tissues, which was meaningfully associated with tumor progression and poor prognosis in patients with CRC. Loss-of-function studies revealed that ZNF280A knockdown inhibited the development and progression of CRC as evident by the inhibition of cell proliferation, colony formation, cell apoptosis, cell cycle distribution, and cell migration in vitro and the repressed tumorigenesis of CRC cells in vivo. Next, we showed that RPS14 was the downstream target of ZNF280A and ZNF280A knockdown promoted the ubiquitination as well as degradation of RPS14 in CRC. Additionally, we demonstrated that RPS14 regulated the development of CRC via PI3K-Akt signaling pathway. Taken together, our findings provide a novel clear insight into ZNF280A/RPS14/PI3K-Akt axis in CRC for the first time, offering a potential target for early detection, diagnosis and treatment of CRC in future clinical applications.

Combined analysis of imaging tumor capsule with imaging tumor size guides the width of resection margin for solitary hepatocellular carcinoma.

BACKGROUND: The optimal width of resection margin (RM) for hepatocellular carcinoma (HCC) remains controversial. This study aimed to investigate the value of imaging tumor capsule (ITC) and imaging tumor size (ITS) in guiding RM width for patients with HCC. METHODS: Patients who underwent hepatectomy for HCC in our center were retrospectively reviewed. ITC (complete/incomplete) and ITS (≤ 3 cm/> 3 cm) were assessed by preoperative magnetic resonance imaging (MRI). Using subgroup analyses based on ITC and ITS, the impact of RM width [narrow RM (< 5 mm)/wide RM (≥ 5 mm)] on recurrence-free survival (RFS), overall survival (OS), and RM recurrence was analyzed. RESULTS: A total of 247 patients with solitary HCC were included. ITC and ITS were independent predictors for RFS and OS in the entire cohort. In patients with ITS ≤ 3 cm, neither ITC nor RM width showed a significant impact on prognosis, and the incidence of RM recurrence was comparable between the narrow RM and wide RM groups (15.6% vs. 4.3%, P = 0.337). In patients with ITS > 3 cm and complete ITC, the narrow RM group exhibited comparable RFS, OS, and incidence of RM recurrence with the wide RM group (P = 0.606, 0.916, and 0.649, respectively). However, in patients with ITS > 3 cm and incomplete ITC, the wide RM group showed better RFS and OS and a lower incidence of RM recurrence compared with the narrow RM group (P = 0.037, 0.018, and 0.046, respectively). CONCLUSIONS: As MRI-based preoperative markers, conjoint analysis of ITC with ITS aids in determining RM width for solitary HCC patients. Narrow RM is applicable in patients with ITS ≤ 3 cm regardless of ITC status and in those with ITS > 3 cm and complete ITC. Wide RM is preferred in those with ITS > 3 cm and incomplete ITC.

High-background parenchymal enhancement in the contralateral breast is an imaging biomarker for favorable prognosis in patients with triple-negative breast cancer treated with chemotherapy.

This study aimed to analyze the association between background parenchymal enhancement (BPE) in the contralateral breast tissue on magnetic resonance imaging (MRI) and clinicopathologic parameters in patients with unilateral breast carcinoma and to investigate its potential prognostic significance. A total of 467 patients who were pathologically confirmed to have unilateral breast cancer and underwent breast MRI were recruited to participate in this cohort study. BPE was assessed in the healthy contralateral breast. Minimal and mild levels were classified as low BPE, whereas moderate and marked levels were classified as high BPE. The effects of BPE on clinicopathologic parameters, overall survival (OS), and invasive disease-free survival (IDFS) were determined. Among the 467 patients, 327 cases were classified into the low-BPE group, whereas 140 cases were classified into the high-BPE group. The high-BPE pattern markedly correlated with age at diagnosis, menopausal status, histologic grading, and estrogen receptor status. BPE pattern did not correlate with OS and IDFS in the entire breast cancer cohort, regardless of whether adjuvant chemotherapy was received. Notably, BPE in the healthy contralateral breast on MRI is markedly related to OS and IDFS in triple-negative breast cancer (TNBC) cases who received chemotherapy. High BPE is related to chemotherapeutic benefits and can be an independent favorable prognostic factor for TNBC patients. Thus, our observations suggest that high BPE pattern can potentially be used as an imaging biomarker for relatively favorable prognosis in TNBC cases receiving chemotherapy. However, the findings need to be verified in a large-scale study.

MRP8/14 mediates macrophage efferocytosis through RAGE and Gas6/MFG-E8, and induces polarization via TLR4-dependent pathway.

Myeloid-related protein 8/14 (MRP8/14) participates in various inflammatory responses, however, its effect on macrophage efferocytosis remains unclear. Here, we demonstrate that MRP8/14 significantly inhibits the efferocytosis of apoptotic thymocytes by mouse bone marrow-derived macrophages (BMDMs), which later proves to be associated with the receptor for advanced glycation end products (RAGE) or for reducing the expression of growth arrest-specific protein 6 and milk fat globule epidermal growth factor 8, independent of RAGE. Furthermore, MRP8/14 promotes polarization of BMDMs from the M2 - to M1 -like phenotype by upregulating expression of M1 -related surface receptor proteins and signature M1 -marker genes and by downregulating signature M2 -marker gene expression, which depends on Toll-like receptor 4 and p38 mitogen-activated protein kinase/nuclear factor κB pathways. Thus, we report a significant inhibitory effect of MRP8/14 on macrophage efferocytosis and MRP8/14-mediated phenotypic polarization, which may be helpful in developing novel therapeutic strategies leading to inflammation resolution.

Reabsorption of bile acids regulated by FXR-OATP1A2 is the main factor for the formation of cholesterol gallstone.

The purpose of this study was to demonstrate the aberrant metabolism of bile acids in patients with cholesterol gallstone and explore for its underlying mechanisms. The composition of bile acids collected from the patients with cholelithiasis and the control individuals was analyzed by LC-MS. The expression of genes regulating the metabolism of bile acids was quantitatively determined by real-time PCR or Western blot analysis. Cholesterol saturation index of patients with gallstone was significantly higher than that of the controls. The concentrations of taurodeoxycholic acid and taurolithocholic acid in the bile of patients were significantly higher than that of the controls. When compared with the controls, it was remarkable in the patients that the mRNA expression of farnesoid X receptor (FXR) was lower, whereas that of organic anion transporting polypeptide (OATP1A2) was higher. However, the expressions of both mRNA and protein of cytochrome P-450 family 8 subfamily B member 1 (CYP8B1) did not differ between the patients and the controls. Although the protein level of CYP8B1 was significantly lower in the subjects with single nucleotide polymorphism (SNP) rs3732860(G), the composition of bile acids and the ratio of CA to CDCA remained unaltered in the patients with different SNP genotype of CYP8B1. In conclusion, the axis of FXR-OATP1A2 that physiologically regulated the reabsorption of bile acids might play an important role in the composition of bile acids and the development of gallstone. CYP8B1 gene was irrelevant to the altered composition of bile acids in patients with gallstone.NEW & NOTEWORTHY For the first time, our results indicate that the axis of farnesoid X receptor-organic anion transporter polypeptide 1A2 that physiologically regulates the reabsorption of bile acids might play an important role in the regulation of the composition of bile acids and make contribution to the development of cholelithiasis.

MicroRNA-107 may regulate lung cancer cell proliferation and apoptosis by targeting TP53 regulated inhibitor of apoptosis 1.

Lung cancer causes over 1.6 million mortalities worldwide annually. MicroRNAs (miRs) are involved in various types of cancer-associated processes. The present study investigated the possible mechanism of miR-107 in the development of lung cancer in order to identify novel targets for clinical treatment. The expression levels of miR-107 and its putative target gene TP53 regulated inhibitor of apoptosis 1 (TRIAP1) were measured in lung cancer tumor tissues and non-tumor adjacent tissues. Subsequently, the association between TRIAP1 and miR-107 was investigated using a dual-luciferase reporter assay. Following transfection, the effects of miR-107 and TRIAP1 on the proliferation and apoptosis of lung cancer cell lines in vitro were investigated using Cell Counting Kit-8 and flow cytometry assays, respectively. Furthermore, the regulatory effect of miR-107 on the expression levels of TRIAP1 and associated proteins was analyzed using a western blot assay. The results revealed lower expression levels of miR-107 and higher expression levels of TRIAP1 in lung cancer tumor tissues compared with non-tumor adjacent tissues. The dual-luciferase reporter assay demonstrated that TRIAP1 is a target gene of miR-107. Additionally, the results revealed that overexpression of miR-107 resulted in a lower proliferation rate and higher apoptosis rate of A549 cells, compared with the negative control (NC) and control groups (P<0.01). The variation of cell proliferation and apoptosis induced by miR-107 mimics was reversed by co-transfection with pcDNA3.1-TRIAP1. Furthermore, the expression levels of cyclin D1 and proliferating cell nuclear antigen were markedly decreased in the miR-107 mimics group compared with the NC group (P<0.01). The expression levels of BCL2 associated X apoptosis regulator, tumor protein p53 and caspase 3 were upregulated and the expression levels of TRIAP1 and BCL2 apoptosis regulator were significantly reduced in the miR-107 mimics group compared with the NC group (P<0.01). The results of the present study suggested that miR-107 regulates lung cancer cell proliferation and apoptosis by targeting TRIAP1.

Soyasaponin II protects against acute liver failure through diminishing YB-1 phosphorylation and Nlrp3-inflammasome priming in mice.

Acute liver failure is characterized by the rapid development of liver dysfunction and remarkably high mortality. Accumulating evidence suggests that soyasaponin possesses potential anti-inflammatory activities. Here, we aimed to investigate the potential role of soyasaponin II in acute liver failure and establish the underlying mechanism. Methods: Lipopolysaccharide/D-galactosamine (LPS/GalN) was employed to induce acute liver failure. We applied liquid chromatography and mass spectrometry (LC/MS) to characterize the changes of soyasaponin II levels in the cecal content and liver. Transcriptomics and proteomics analysis were used to evaluate the functional molecule mediated by soyasaponin II in macrophages. Results: LPS/GalN administration markedly decreased fecal and hepatic soyasaponin II levels. Soyasaponin II treatment protected mice against LPS/GalN induced acute liver injury. Additionally, soyasaponin II markedly diminished Y-Box Binding Protein 1 (YB-1) phosphorylation and nuclear translocation, Nlrp3 inflammasome priming, and interleukin 1ß (Il-1ß) production in macrophages. Phosphorylated YB-1 could activate Nlrp3 mRNA transcription by binding the promoter region. Finally, immunofluorescence analysis showed elevated p-YB-1 nuclear translocation in macrophages of acute liver failure patients compared to controls. Conclusion: Our data shows that soyasaponin II which serves as a novel inhibitor for YB-1 phosphorylation and Nlrp3 inflammasome priming could protect mice against LPS/GalN induced acute liver failure.

Study on the activity and mechanism of skimmianine against human non-small cell lung cancer.

The present research was to investigate the effects of skimmianine (SK) in four non-small cell lung cancer (NSCLC) cells. We found that SK can significantly inhibit the growth of NSCLC cells and markedly induce apoptosis in NSCLC cells. The effects of growth inhibition and apoptosis induction were in a concentration-response relationship and caspase-dependent manner.

Knockdown of miR­935 increases paclitaxel sensitivity via regulation of SOX7 in non­small­cell lung cancer.

Sex determining region Y­box (SOX)7 is a member of the SOX family and is responsible for various developmental processes. As a tumor suppressor, decreased expression of SOX7 has been observed in several cancer types, including non­small­cell lung cancer (NSCLC). However, the mechanism underlying SOX7 downregulation and its role in chemoresistance in NSCLC remains poorly understood. In the present study, the inhibition of microRNA (miR)­935 increased the expression of SOX7 at the mRNA and protein levels in A549 cells. The luciferase reporter assay verified that miR­935 could directly bind to the 3'untranslated region of SOX7 mRNA to suppress its expression in A549 cells. In addition, the inhibition of miR­935 enhanced the anticancer effect of paclitaxel, i.e., induced cell growth arrest and apoptosis in A549 cells. It was further observed that the inhibition of miR­935 decreased the B cell lymphoma (Bcl)­2 and phosphorylated­RAC­α serine/threonine­protein kinase (AKT) protein levels and increased the Bcl­2 associated X, apoptosis regulator protein levels, without affecting the AKT levels in the presence of paclitaxel within A549 cells. The findings of the present study validate miR­935 as a predictor of paclitaxel sensitivity in NSCLC.

Alpha-Lipoic Acid Suppresses Extracellular Histone-Induced Release of the Infammatory Mediator Tumor Necrosis Factor-α by Macrophages.

BACKGROUND/AIMS: This study investigated signaling pathways via which extracellular histones induce the pro-inflammatory cytokine tumor necrosis factor-α (TNF-α) release from the macrophage cell line RAW 264.7 and the anti-inflammatory efficacy of the antioxidant alpha-lipoic acid (ALA). METHODS: ELISA and western blotting analyses were conducted to detect the release of TNF-α from histone-stimulated RAW 264.7 macrophages and the associated phospho-activation of MAPKs (ERK and p38) and NF-κB p65. The effects of ALA on the release of TNF-α and phospho-activation of the MAPKs and NF-κB p65 were studied. P < 0.05 was considered statistically significant. RESULTS: Extracellular histones dose-dependently induced TNF-α release from RAW 264.7 cells and increased the phosphorylation of p38, ERK, and NF-κB p65. TNF-α release was markedly suppressed by p38, ERK, and NF-kB inhibitors. ALA reduced histone-induced TNF-α release, ERK/p38 MAPK activation, and NF-kB activation without affecting macrophage viability. CONCLUSION: Histones induce TNF-α release from macrophages by activating the MAPK and NF-kB signaling pathways, while ALA suppresses this response by inhibiting ERK, p38 and NF-kB. These findings identify potentially critical inflammatory signaling pathways in sepsis and molecular targets for sepsis treatment.

Polydatin post-treatment alleviates myocardial ischaemia/reperfusion injury by promoting autophagic flux.

Polydatin (PD), a resveratrol (RES) glycoside, has a stronger antioxidative effect than RES. It is known that RES is an autophagic enhancer and exerts a cardioprotective effect against ischaemia/reperfusion (I/R) injury. However, the effect of PD post-treatment on myocardial I/R injury remains unclear. In the present study, we investigated the influences of PD post-treatment on myocardial I/R injury and autophagy. C57BL/6 mice underwent left coronary artery (LCA) occlusion and cultured neonatal rat cardiomyocytes (NRCs) subjected to hypoxia were treated with vehicle or PD during reperfusion or re-oxygenation. We noted that PD enhanced autophagy and decreased apoptosis during I/R or hypoxia/reoxygenation (H/R), and this effect was antagonized by co-treatment with adenovirus carrying short hairpin RNA for Beclin 1 and 3-methyladenine (3-MA), an autophagic inhibitor. Compared with vehicle-treated mice, PD-treated mice had a significantly smaller myocardial infarct size (IS) and a higher left ventricular fractional shortening (LVFS) and ejection fraction (EF), whereas these effects were partly reversed by 3-MA. Furthermore, in the PD-treated NRCs, tandem fluorescent mRFP-GFP-LC3 assay showed abundant clearance of autophagosomes with an enhanced autophagic flux, and co-treatment with Bafilomycin A1 (Baf), a lysosomal inhibitor, indicated that PD promoted the degradation of autolysosome. In addition, PD post-treatment reduced mitochondrial membrane potential and cellular reactive oxygen species (ROS) production in NRCs, and these effects were partially blocked by Baf. These findings indicate that PD post-treatment limits myocardial I/R injury by promoting autophagic flux to clear damaged mitochondria to reduce ROS and cell death.

Could Tumor Size Be A Predictor for Papillary Thyroid Microcarcinoma: a Retrospective Cohort Study.

BACKGROUND: Central lymph node metastasis(CLNM) is common in papillary thyroid microcarcinoma (PTMC). The aim of this study was to define the pathohistologic risk grading based on surgical outcomes. MATERIALS AND METHODS: Statistical analysis was performed to figure out the optimal cut-off values of size in preoperative ultrasound images for defining the risk of CLNM in papillary thyroid microcarcinoma. Receiver operating characteristic curves (ROC) studies were carried out to determine the cutoff value(s) for the predictor(s). All the patients were divided into two groups according to the above size and the clinic-pathological and immunohistochemical parameters were compared to determine the significance of findings. RESULTS: The optimal cut-off value of tumor size to predict the risk of CLNM in papillary thyroid microcarcinoma was 0.575 cm (area under the curve 0.721) according to the ROC curves. Significant differences were observed on the multifocality, extrathyroidal extension and central lymph node metastasis between two groups which were divided according to the tumor size by the cutoff values. Patients in two groups showed different positive rate and intensity of Ki67. CONCLUSIONS: The size of PTMC in ultrasound images are helpful to predict the aggressiveness of the tumors, it could be an easy predictor for PTMC prognosis and assist us to choose treatment.

Combined downregulation of microRNA-133a and microRNA-133b predicts chemosensitivity of patients with esophageal squamous cell carcinoma undergoing paclitaxel-based chemotherapy.

microRNA-133a (miR-133a) and miR-133b, located on chromosome 18 in the same bicistronic unit, have been commonly identified as being downregulated in esophageal squamous cell carcinoma (ESCC). The aim of this study was to investigate the correlation of miR-133a/b expression with efficacy of paclitaxel-based chemotherapy and clinical outcome of ESCC patients. miR-133a expression and miR-133b expression were examined in 100 newly diagnosed ESCC patients prior to treatment by quantitative real-time PCR. Then, the patients received four cycles of paclitaxel-based chemotherapy, the short-term treatment efficacy was evaluated, and a 3-year follow-up was performed. Expression levels of miR-133a and miR-133b were both significantly lower in ESCC tissues compared to adjacent noncancerous tissues (both P < 0.001). In addition, combined miR-133a/b downregulation was found to be closely correlated with advanced tumor stage (P = 0.02) and poor differentiation (P = 0.01). Moreover, the response rate of ESCC patients to paclitaxel-based chemotherapy was significantly higher in combined miR-133a/b downregulation group compared with other groups (P = 0.02). Furthermore, univariate and multivariate Cox analyses revealed that tumor stage and combined expression of miR-133a/b were independent prognosis factors in ESCC patients. Our data offer the convincing evidence that combined expression of miR-133a and miR-133b may predict chemosensitivity of patients with ESCC undergoing paclitaxel-based chemotherapy, implying its importance in applying 'personalized cancer medicine' in the clinical treatment of ESCC. We also identified combined expression of miR-133a and miR-133b as an effective prognostic marker of this malignancy.

[Research of rat small intestinal mesentery lymphoid tissue stimulating allograft mixed lymphocyte reaction].

OBJECTIVE: To evaluate the effect of the small intestinal mesenteric lymphoid tissues stimulating mixed lymphocyte reaction with dendritic cells (DC) and peripheral blood monocyte cells (PBMC), and observe the changes of the MHC molecular expression on DC. METHODS: DC, PBMC and mixed lymphocyte were separated to culture from SD rats. Lymphoid tissue suspension was adopted from small intestinal mesentery of Wistar rats. In the mixed lymphocyte reaction (MLR), the cellular proliferation of small intestinal mesenteric lymphoid tissue antigen act on DC and PBMC was detected with cell counting of CCK-8 assay, the same assay used in small intestinal mesenteric lymphoid tissue antigen and ovalbumin (OVA) acting on DC. FACS analysis was performed after lymphoid tissue suspension stimulating DC to observe the MHC molecular expression. RESULTS: In the lymphoid tissue suspension, 91% of the cells was lymphocyte, others including granulocyte, plasmocyte, epithelium. The effect of stimulating mixed lymphocyte proliferation were higher in DC groups than in PBMC groups with the small intestinal mesenteric lymphoid tissue (P < 0.05). In the proportion of DC and mixed lymphocyte >or= 1:100 groups, the mixed lymphocyte proliferation were higher in the small intestinal mesenteric lymphoid tissues groups than in the OVA groups (P < 0.05). After stimulated by the small intestinal mesenteric lymphoid tissue, DC expressed higher MHC-I and -II molecules than control groups. CONCLUSIONS: The small intestinal mesenteric lymphoid tissue has high antigenicity; the antigen presenting ability of DC was much stronger than granulocytes; DC expresses high MHC-I and MHC-II molecules after stimulated by mixed lymphoid tissue suspension.

[Clinical analysis of infectious complications following abdominal cluster transplantation].

OBJECTIVE: To investigate the characteristic and management of postoperative infection in abdominal cluster transplantation. METHODS: Preliminary experience of two cases of abdominal cluster transplantation including small intestine was reviewed. RESULTS: Combination of five immunosuppressive agents based on tacrolimus was used. Severe Gram-negative bacillus infections occurred. The majority of invasive fungal infections was due to Candida species. Cytomegalovirus (CMV) infection increased monocytes and caused eosinopenia and an inversion of the CD4(+) to CD8(+) cell ratio in recipient I, and human CMV matrix proteins pp71 (CMV-pp71) was detected and identified in bile by PCR. Microabscesses in liver transplant biopsies were presented. CONCLUSIONS: Infectious complications after cluster transplantation were complicated. Strategies to optimize the immunity suppression protocol and early diagnosis and treatment will be important to reduce infection after abdominal cluster transplantation.