Identifying patterns of immune related cells and genes in the peripheral blood of acute myocardial infarction patients using a small cohort.

BACKGROUND: The immune system plays a vital role in the pathophysiology of acute myocardial infarction (AMI). However, the exact immune related mechanism is still unclear. This research study aimed to identify key immune-related genes involved in AMI. METHODS: CIBERSORT, a deconvolution algorithm, was used to determine the proportions of 22 subsets of immune cells in blood samples. The weighted gene co-expression network analysis (WGCNA) was used to identify key modules that are significantly associated with AMI. Then, CIBERSORT combined with WGCNA were used to identify key immune-modules. The protein-protein interaction (PPI) network was constructed and Molecular Complex Detection (MCODE) combined with cytoHubba plugins were used to identify key immune-related genes that may play an important role in the occurrence and progression of AMI. RESULTS: The CIBERSORT results suggested that there was a decrease in the infiltration of CD8 + T cells, gamma delta (γδ) T cells, and resting mast cells, along with an increase in the infiltration of neutrophils and M0 macrophages in AMI patients. Then, two modules (midnightblue and lightyellow) that were significantly correlated with AMI were identified, and the salmon module was found to be significantly associated with memory B cells. Gene enrichment analysis indicated that the 1,171 genes included in the salmon module are mainly involved in immune-related biological processes. MCODE analysis was used to identify four different MCODE complexes in the salmon module, while four hub genes (EEF1B2, RAC2, SPI1, and ITGAM) were found to be significantly correlated with AMI. The correlation analysis between the key genes and infiltrating immune cells showed that SPI1 and ITGAM were positively associated with neutrophils and M0 macrophages, while they were negatively associated with CD8 + T cells, γδ T cells, regulatory T cells (Tregs), and resting mast cells. The RT-qPCR validation results found that the expression of the ITGAM and SPI1 genes were significantly elevated in the AMI samples compared with the samples from healthy individuals, and the ROC curve analysis showed that ITGAM and SPI1 had a high diagnostic efficiency for the recognition of AMI. CONCLUSIONS: Immune cell infiltration plays a crucial role in the occurrence and development of AMI. ITGAM and SPI1 are key immune-related genes that are potential novel targets for the prevention and treatment of AMI.

Machine learning-based prediction of invisible intraprostatic prostate cancer lesions on 68 Ga-PSMA-11 PET/CT in patients with primary prostate cancer.

PURPOSE: 68 Ga-PSMA PET/CT has high specificity and sensitivity for the detection of both intraprostatic tumor focal lesions and metastasis. However, approximately 10% of primary prostate cancer are invisible on PSMA-PET (exhibit no or minimal uptake). In this work, we investigated whether machine learning-based radiomics models derived from PSMA-PET images could predict invisible intraprostatic lesions on 68 Ga-PSMA-11 PET in patients with primary prostate cancer. METHODS: In this retrospective study, patients with or without prostate cancer who underwent 68 Ga-PSMA PET/CT and presented negative on PSMA-PET image at either of two different institutions were included: institution 1 (between 2017 and 2020) for the training set and institution 2 (between 2019 and 2020) for the external test set. Three random forest (RF) models were built using selected features extracted from standard PET images, delayed PET images, and both standard and delayed PET images. Then, subsequent tenfold cross-validation was performed. In the test phase, the three RF models and PSA density (PSAD, cut-off value: 0.15 ng/ml/ml) were tested with the external test set. The area under the receiver operating characteristic curve (AUC) was calculated for the models and PSAD. The AUCs of the radiomics model and PSAD were compared. RESULTS: A total of 64 patients (39 with prostate cancer and 25 with benign prostate disease) were in the training set, and 36 (21 with prostate cancer and 15 with benign prostate disease) were in the test set. The average AUCs of the three RF models from tenfold cross-validation were 0.87 (95% CI: 0.72, 1.00), 0.86 (95% CI: 0.63, 1.00), and 0.91 (95% CI: 0.69, 1.00), respectively. In the test set, the AUCs of the three trained RF models and PSAD were 0.903 (95% CI: 0.830, 0.975), 0.856 (95% CI: 0.748, 0.964), 0.925 (95% CI:0.838, 1.00), and 0.662 (95% CI: 0.510, 0.813). The AUCs of the three radiomics models were higher than that of PSAD (0.903, 0.856, and 0.925 vs. 0.662, respectively; P = .007, P = .045, and P = .005, respectively). CONCLUSION: Random forest models developed by 68 Ga-PSMA-11 PET-based radiomics features were proven useful for accurate prediction of invisible intraprostatic lesion on 68 Ga-PSMA-11 PET in patients with primary prostate cancer and showed better diagnostic performance compared with PSAD.

Genetic characteristics and ploidy trigger the high inducibility of double haploid (DH) inducer in Brassica napus.

BACKGROUND: Our recently reported doubled haploid (DH) induction lines e.g., Y3380 and Y3560 are allo-octoploid (AAAACCCC, 2n = 8× ≈ 76), which can induce the maternal parent to produce DH individuals. Whether this induction process is related to the production of aneuploid gametes form male parent and genetic characteristics of the male parent has not been reported yet. RESULTS: Somatic chromosome counts of DH inducer parents, female wax-less parent (W1A) and their F1 hybrid individuals revealed the reliability of flow cytometry analysis. Y3560 has normal chromosome behavior in metaphase I and anaphase I, but chromosome division was not synchronized in the tetrad period. Individual phenotypic identification and flow cytometric fluorescence measurement of F1 individual and parents revealed that DH individuals can be distinguished on the basis of waxiness trait. The results of phenotypic identification and flow cytometry can identify the homozygotes or heterozygotes of F1 generation individuals. The data of SNP genotyping coupled with phenotypic waxiness trait revealed that the genetic distance between W1A and F1 homozygotes were smaller as compared to their heterozygotes. It was found that compared with allo-octoploids, aneuploidy from allo-octoploid segregation did not significantly increase the DH induction rate, but reduced male infiltration rate and heterozygous site rate of induced F1 generation. The ploidy, SNP genotyping and flow cytometry results cumulatively shows that DH induction is attributed to the key genes regulation from the parents of Y3560 and Y3380, which significantly increase the induction efficiency as compared to ploidy. CONCLUSION: Based on our findings, we hypothesize that genetic characteristics and aneuploidy play an important role in the induction of DH individuals in Brassca napus, and the induction process has been explored. It provides an important insight for us to locate and clone the genes that regulate the inducibility in the later stage.

Maternal karyogene and cytoplasmic genotype affect the induction efficiency of doubled haploid inducer in Brassica napus.

BACKGROUND: Artificial synthesis of octoploid rapeseed double haploid (DH) induction lines Y3380 and Y3560 was made possible by interspecific hybridization and genome doubling techniques. Production of pure lines by DH induction provides a new way to achieve homozygosity earlier in B.napus. Previously, the mechanism of induction, and whether the induction has obvious maternal genotypic differences or not, are not known so far. RESULTS: In this study, different karyogene and cytoplasmic genotype of B.napus were pollinated with the previously reported DH inducers e.g. Y3380 and Y3560. Our study presents a fine comparison of different cytoplasmic genotypes hybridization to unravel the mechanism of DH induction. Ploidy identification, fertility and SSR marker analysis of induced F1 generation, revealed that ploidy and phenotype of the induced F1 plants were consistent with that type of maternal, rather than paternal parent. The SNP chip analysis revealed that induction efficiency of DH inducers were affected by the karyogene when the maternal cytoplasmic genotypes were the same. However, DH induction efficiency was also affected by cytoplasmic genotype when the karyogenes were same, and the offspring of the ogura cytoplasm showed high frequency inducer gene hybridization or low-frequency infiltration. CONCLUSION: The induction effect is influenced by the interaction between maternal karyogene and cytoplasmic genotype, and the results from the partial hybridization of progeny chromosomes indicate that the induction process may be attributed to the selective elimination of paternal chromosome. This study provides a basis for exploring the mechanism of DH inducer in B.napus, and provides new insights for utilization of inducers in molecular breeding.

Surgery of the Primary Tumor Offers Survival Benefits of Breast Cancer with Synchronous Ipsilateral Supraclavicular Lymph Node Metastasis.

BACKGROUND: Controversy exists around the locoregional management of the primary tumor for breast cancer associated with synchronous ipsilateral supraclavicular lymph node metastasis (sISLM) due to the rarity of the disease and limited available data. This study aimed to compare outcomes of patients in the Surveillance, Epidemiology, and End Results (SEER) database with sISLM who underwent surgical resection and radiation of the primary tumor with those who did not. METHODS: This population-based retrospective study included breast cancer patients with sISLM without distant metastases from 2004 to 2016 in the SEER database. In this study, patients had been stratified by operative management, and propensity score matching (PSM) had been successfully applied. RESULTS: A total of 1172 breast cancer patients with sISLM were included in the study: 863 (73.6%) of patients underwent the primary tumor resection, and 309 (26.4%) patients did not undergo surgery. The median survival time in the surgery group was longer compared to the nonsurgery group in the overall cohort and the PSM cohort. We concluded that the primary tumor resection was associated with improved survival. Subgroup analysis further demonstrated that local surgery was not inferior to radical surgery. CONCLUSION: For selected breast cancer patients with sISLM, surgery is a promising local intervention which may improve the survival.

ACO2 and ANPEP as novel prognostic markers for gallbladder squamous cell/adenosquamous carcinomas and adenocarcinomas.

BACKGROUND: Squamous cell/adenosquamous carcinoma (SC/ASC) is a rarely identified form of gallbladder cancer with poorly understood clinical features. As such, there is an urgent need to identify novel prognostic biomarkers for such gallbladder SC/ASC cases, and for gallbladder adenocarcinomas (ACs). METHODS: The levels of ACO2 and ANPEP proteins were assessed via an EnVision-based immunohistochemical approach using 46 SC/ASC and 80 AC patient samples. RESULTS: There was a marked reduction in levels of ACO2 and ANPEP in gallbladder AC relative to normal adjacent tissue or benign gallbladder lesions. The was a significant correlation between lack of ACO2 and ANPEP and larger tumors, higher tumor-node-metastasis (TNM) staging, invasion, metastasis to regional lymph nodes, and ineligibility for surgical resection in both SC/ASC and AC tumor samples. Kaplan-Meier survival analyses further confirmed a relationship between ACO2 and ANPEP negativity and decreased overall survival in patients with these diseases (p < 0.05 or p < 0.01), and a multivariate regression analysis further established that ACO2 negativity and ANPEP negativity were independently predictive of poor SC/ASC and AC patient outcomes. CONCLUSIONS: ACO2 and ANPEP may have key physiological relevance in cancers of the gallbladder and thus warrant investigation as prognostic biomarkers.

The role of 99mTc-MIBI SPECT/CT in patients with secondary hyperparathyroidism: comparison with 99mTc-MIBI planar scintigraphy and ultrasonography.

BACKGROUND: This study aimed to compare the sensitivity of 99mTc-MIBI SPECT/CT, 99mTc-MIBI planar scintigraphy and ultrasonography (US) in patients with secondary hyperparathyroidism (SHPT), and to explore the factors that affect the sensitivity of 99mTc-MIBI SPECT/CT. METHODS: In this retrospective study, forty-six patients with SHPT who underwent 99mTc-MIBI planar scintigraphy, 99mTc-MIBI SPECT/CT and US were enrolled. They underwent surgery within 1 month. We compared the sensitivity of the different imaging methods based on the lesions according to the pathological results. The parathyroid lesions on 99mTc-MIBI SPECT/CT images were divided into missed diagnosis group (MDG) and non-missed diagnosis group (NMDG). We compared the lesion to background ratio (LBR), maximum diameter, volume, the mean CT Hounsfield unit values (CTmean) and location of lesions between MDG and NMDG. RESULTS: The sensitivity of 99mTc-MIBI SPECT/CT, 99mTc-MIBI planar scintigraphy and US were 70.30% versus 48.48% versus 61.82%, respectively. The sensitivity of 99mTc-MIBI SPECT/CT combined US was 79.39%, which was higher than 99mTc-MIBI SPECT/CT with significant difference (P = 0.000). On 99mTc-MIBI SPECT/CT images, the LBR, maximum diameter and volume of lesions in MDG was smaller than those in NMDG with significant difference (P < 0.001). The average LBR, maximum diameter and volume of lesions in MDG and NMDG were 3.42 ± 1.28, 9.32 ± 2.69 mm, 208.51 ± 163.22 mm3 versus 6.75 ± 5.08, 15.03 ± 4.94 mm and 863.85 ± 1216.0 mm3, respectively. CONCLUSIONS: 99mTc-MIBI SPECT/CT exhibited the highest sensitivity among the three methods. When 99mTc-MIBI SPECT/CT combined with US, the sensitivity can be further improved. Lesions with lower MIBI uptake and smaller lesions on 99mTc-MIBI SPECT/CT images were easily missed.

Downregulated microRNA-330 suppresses left ventricular remodeling via the TGF-ß1/Smad3 signaling pathway by targeting SRY in mice with myocardial ischemia-reperfusion injury.

microRNAs (miRs) are essential in the development of heart failure. The aim of this study is to investigate the effect of microRNA-330 (miR-330) on left ventricular remodeling via the TGF-ß1/Smad3 signaling pathway by targeting the sex-determining region Y (SRY) in mice with myocardial ischemia-reperfusion injury (MIRI). Differentially expressed gene (DEG) in myocardial ischemia-reperfusion (IR) was screened out and the miR that targeted the DEG was also predicted and verified. A model of MIRI was established to detect the expression of miR-330, SRY, transforming growth factor-ß (TGF-ß1), and Sekelsky mothers against dpp3 (Smad3). To further investigate the role of miR-330 in MIRI with the involvement of SRY and TGF-ß1/Smad3 signaling pathway, the modeled mice were treated with different mimic, inhibitor, or small interfering RNA (siRNA) to observe the changes of the related gene expression, as well as the myocardial infarction size and volume of myocardial collagen. SRY was screened out and verified as a target gene of miR-330. The MIRI mice showed enlarged myocardial infarction size, increased volume of myocardial collagen, increased expression of miR-330, TGF-ß1 and Smad3, while decreased the expression of SRY. The MIRI mice treated with miR-330 inhibitor showed decreased myocardial infarction size, the volume of myocardial collagen, and expression of TGF-ß1 and Smad3 but promoted expression of SRY. Our findings demonstrated that downregulated miR-330 could suppress left ventricular remodeling to inhibit the activation of the TGF-ß1/Smad3 signaling pathway via negatively targeting of SRY in mice with MIRI. This can be a potential target in the strategy to attenuate patient suffering.

A Case of Renal Involvement in B Lymphoblastic Lymphoma Leukemia.

BACKGROUND: Renal involvement is rare in B lymphoblastic lymphoma (B-LBL). The authors describe a rare case of renal involvement in a 21-year-old male patient with B lymphoblastic lymphoma leukemia, presenting with severe lactic acidosis. METHODS: Hematologic investigation, bone marrow aspirate and biopsy, cytogenetic analysis and renal biopsy were performed. RESULTS: The patient achieved complete hematological remission (CHR) after induction therapy with the regimen of VDCP and received consolidation chemotherapy regularly. He remained CHR until now. CONCLUSIONS: Renal biopsy, bone marrow aspirate, and biopsy are important to confirm a correct diagnosis. Renal involvement in B-LBL as a prognostic factor needs further studies.

Maternal doubled haploid production in interploidy hybridization between Brassica napus and Brassica allooctaploids.

MAIN CONCLUSION: We found a new in vivo route to produce maternal doubled haploid of Brassica napus . The pollen donor, an allooctaploid rapeseed, acts as a DH inducer. Inbred line has a powerful advantage in cultivar breeding and genetic analysis. Compared to the traditional breeding methods, doubled haploid production can save years off the breeding process. Though genotype-dependent tissue culture methods are widely used in the Brassica crops, seed-based in vivo doubled haploid developing systems are rare in nature and in the laboratory. As interspecific cross and interploid hybridization play an important role in genome evolution and plant speciation, we created a new Brassica artificial hybrid, a Brassica allooctaploid (AAAACCCC, 2n = 8× = 76), by interspecific crossing and genome doubling. A homozygous line was observed at the third self-generation of a synthesized Brassica allohexaploid (AAAACC, 2n = 6× = 58). Crosses between B. napus as female and Brassica allooctaploid as pollen donor were conducted, which yielded maternal doubled haploid B. napus that were identified based on phenotype, ploidy, and molecular analysis. The Brassica octaploid acted as a maternal doubled haploid inducer and had a relatively high induction rate. Our research provides a new insight for generation of homozygous lines in vivo using a single-step approach, as well as promotes the understanding in breeding programs and genetic studies involving the Brassicas.

Chemotherapy-driven increases in the CDKN1A/PTN/PTPRZ1 axis promote chemoresistance by activating the NF-κB pathway in breast cancer cells.

BACKGROUND: Chemotherapy is the primary established systemic treatment for patients with breast cancer, especially those with the triple-negative subtype. Simultaneously, the resistance of triple-negative breast cancer (TNBC) to chemotherapy remains a major clinical problem. Our previous study demonstrated that the expression levels of PTN and its receptor PTPRZ1 were upregulated in recurrent TNBC tissue after chemotherapy, and this increase was closely related to poor prognosis in those patients. However, the mechanism and function of chemotherapy-driven increases in PTN/PTPRZ1 expression are still unclear. METHODS: We compared the expression of PTN and PTPRZ1 between normal breast and cancer tissues as well as before and after chemotherapy in cancer tissue using the microarray analysis data from the GEPIA database and GEO database. The role of chemotherapy-driven increases in PTN/PTPRZ1 expression was examined with a CCK-8 assay, colony formation efficiency assay and apoptosis analysis with TNBC cells. The potential upstream pathways involved in the chemotherapy-driven increases in PTN/PTPRZ1 expression in TNBC cells were explored using microarray analysis, and the downstream mechanism was dissected with siRNA. RESULTS: We demonstrated that the expression of PTN and PTPRZ1 was upregulated by chemotherapy, and this change in expression decreased chemosensitivity by promoting tumour proliferation and inhibiting apoptosis. CDKN1A was the critical switch that regulated the expression of PTN/PTPRZ1 in TNBC cells receiving chemotherapy. We further demonstrated that the mechanism of chemoresistance by chemotherapy-driven increases in the CDKN1A/PTN/PTPRZ1 axis depended on the NF-κB pathway. CONCLUSIONS: Our studies indicated that chemotherapy-driven increases in the CDKN1A/PTN/PTPRZ1 axis play a critical role in chemoresistance, which suggests a novel strategy to enhance chemosensitivity in breast cancer cells, especially in those of the triple-negative subtype.

Expression of UGP2 and CFL1 expression levels in benign and malignant pancreatic lesions and their clinicopathological significance.

BACKGROUND: This study investigated UGP2 (uridine diphosphate-glucose pyrophosphorylase-2) and CFL1 (cofilin-1) expression in pancreatic ductal carcinoma (PDC), paracancerous tissue (PT), benign lesions (BL), and normal tissue (NT) and their clinicopathological significance. METHODS: Surgical specimens, which were collected from 106 cases of pancreatic ductal carcinoma, 35 cases of paracancerous tissues, 55 cases of benign lesions and 13 cases of normal pancreatic tissues, were fixed with 4% formaldehyde to prepare conventional paraffin-embedded sections. EnVision immunohistochemical was used to stain for UGP2 and CFL1. Kaplan-Meier survival analysis was performed to assess the correlation of expression pattern with survival. RESULTS: We found that positive UGP2 and CFL1 expression in PDC were significantly higher than those in PT, BL, and NT. In PT and BL with positive UGP2 and CFL1 expression, mild to severe atypical hyperplasia or intraepithelial neoplasia of grades II-III was observed in ductal epithelium. Positive UGP2 and CFL1 expression in cases with high differentiation, no lymph node metastasis, no surrounding invasion, and TNM (tumor-node-metastasis) staging I or/and II were significantly lower than those in cases with poor differentiation, lymph node metastasis, surrounding invasion, and TNM stage III and/or IV. Positive UGP2 expression in male patients was significantly lower than that in female patients. UGP2 and CFL1 expression in PDC were positively correlated. Kaplan-Meier survival analysis showed the degree of differentiation, tumor maximal diameter, TNM stage, lymph node metastasis, and surrounding invasion, and UGP2 and CFL1 expression were closely related to the average survival time of patients with PDC. The survival time of patients with positive UGP2 and CFL1 expression was significantly shorter than that of patients with negative expression. Cox multivariate analysis showed that poor differentiation, tumor maximal diameter ≥ 3 cm, TNM stage III or IV, lymph node metastasis, surrounding invasion, and positive UGP2 and CFL1 expression was negatively correlated with the postoperative survival rate and positively correlated with the mortality of patients with PDC. CONCLUSION: Positive expression of UGP2 and CFL1 can serve a valuable prognostic factor in pancreatic cancer.

The clinicopathological significance of forkhead box P1 and forkhead box O3a in pancreatic ductal adenocarcinomas.

Pancreatic ductal adenocarcinoma is a highly malignant tumor with poor prognosis, and the biomarkers for the early diagnosis, targeting therapy, and prognosis are still not clinically available. This study investigated the expression of forkhead box P1 and forkhead box O3a proteins in human pancreatic ductal adenocarcinoma tumor tissues and pancreatic tissues with and without benign lesions using immunohistochemical staining. Results showed that the positive rates of forkhead box P1 and forkhead box O3a protein expression were significantly lower in pancreatic ductal adenocarcinoma tumors compared to peritumoral tissues, benign pancreatic tissues, and normal pancreatic tissues (p < 0.01). Pancreatic tissues with negative forkhead box P1 and forkhead box O3a protein expression exhibited dysplasia or intraepithelial neoplasia. The positive rates of forkhead box P1 and forkhead box O3a expression were significantly lower in cases with tumor mass >5 cm, lymph node metastasis, invasion to surrounding tissues and organs, and tumor-node-metastasis III + IV stage disease compared to cases with tumor mass ⩽5 cm (p < 0.05), no lymph node metastasis (p < 0.001 and p = 0.001, respectively), no invasion (p = 0.003 and p = 0.004, respectively), and tumor-node-metastasis I or II stage disease (p < 0.05). Kaplan-Meier survival analysis showed that pancreatic ductal adenocarcinoma patients with negative forkhead box P1 and forkhead box O3a expression survived significantly shorter than patients with positive forkhead box P1 and forkhead box O3a expression (p = 0.000). Cox multivariate analysis revealed that negative forkhead box P1 and forkhead box O3a expression was an independent poor prognosis factor in pancreatic ductal adenocarcinoma patients. The area under the curve of a receiver operating characteristic curve was 0.642 for forkhead box P1 (95% confidence interval: 0.553-0.730) and 0.655 for forkhead box O3a (95% confidence interval: 0.6568-0.742). Loss of forkhead box P1 and forkhead box O3a protein expression is associated with carcinogenesis, progression, and poor prognosis in patients with pancreatic ductal adenocarcinomas.

Soulieoside O, a new cyclolanostane triterpenoid glycoside from Souliea vaginata.

A new cyclolanostane triterpenoid glycoside, soulieoside O (1), together with 25-O-acetylcimigenol-3-O-ß-d-xylopyranoside (2) and cimigenol-3-O-ß-d-xylopyranoside (3), was isolated from the rhizomes of Souliea vaginata. Their structures were characterized by spectroscopic analysis and chemical methods. The new compound showed moderate inhibitory activity against three human cancer cell lines with IC50 values of 9.3-22.5 µM.

Association of chloride intracellular channel 4 and Indian hedgehog proteins with survival of patients with pancreatic ductal adenocarcinoma.

Pancreatic cancer is the fourth most common cause of cancer-related mortality. Novel molecular biomarkers need to be identified for personalized medicine and to improve survival. The aim of this study was to examine chloride intracellular channel 4 (CLIC4) and Indian Hedgehog (Ihh) expression in benign and malignant lesions of the pancreas and to examine the eventual association between CLIC4 and Ihh expression, with clinicopathological features and prognosis of pancreatic cancer. A retrospective study of specimens collected from January 2000 to December 2011 at the Department of Pathology of the Second and Third Xiangya Hospitals, Central South University was undertaken to explore this question. Immunohistochemistry of CLIC4 and Ihh was performed with EnVision™ in 106 pancreatic ductal adenocarcinoma specimens, 35 paracancer samples (2 cm away from the tumour, when possible or available), 55 benign lesions and 13 normal tissue samples. CLIC4 and Ihh expression in pancreatic ductal adenocarcinoma were significantly higher than in paracancer tissue and benign lesions (CLIC4: P = 0.009 and Ihh: P < 0.0001; CLIC4: P = 0.0004 and Ihh: P = 0.0001 respectively). CLIC4 and Ihh expression was negative in normal pancreatic tissues. The expression of CLIC4 and Ihh was associated significantly with tumour grade, lymph node metastasis, tumour invasion and poor overall survival. Thus CLIC4 and Ihh could serve as biological markers for the progression, metastasis and/or invasiveness of pancreatic ductal adenocarcinoma.

SHP2 and UGP2 are Biomarkers for Progression and Poor Prognosis of Gallbladder Cancer.

Biomarkers for the diagnosis, prognosis, and targeting therapy of gallbladder cancers are not clinically available. This study demonstrated that the percentage of cases with positive SHP2 and UGP2 expression significantly correlated with the percentage of cases with positive vimentin, ß-catenin, MMP2, MMP9, and Ki-67 expression, large tumor size, high TNM stage, lymph node metastasis, and survival in patients with adenocarcinomas and squamous cell/adenosquamous carcinomas. Positive SHP2 and UGP2 expression are independent poor-prognostic factors in both types of tumors. Our study suggested that positive SHP2 and UGP2 expression correlated with clinicopathological and biological behaviors, and poor-prognosis of gallbladder cancer.

Jagged1 and DLL4 expressions in benign and malignant pancreatic lesions and their clinicopathological significance.

BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) is characterized by a poor prognosis. Despite intensive research, markers for the early diagnosis, prognosis, and targeting therapy of PDAC are not available. This study aimed to investigate the protein expressions of Jagged1 and DLL4 in PDAC tumor, benign pancreatic and normal pancreatic tissues, and analyze the associations of the two proteins with the clinical and pathological characteristics of PDAC. METHODS: A total of 106 PDAC tumor tissues and 35 peritumoral tissues were collected from January 2000 to December 2011 at our hospitals. Thirteen normal pancreatic tissues and 55 benign pancreatic specimens were collected at the same period. Immunohistochemical staining was used to measure Jagged1 and DLL4 protein expressions in these tissues. RESULTS: The percentage of positive Jagged1 and DLL4 was significantly higher in PDAC than in normal pancreatic tissues, benign pancreatic tissues, and peritumoral tissues (P<0.01). The higher Jagged1 and DLL4 expressions in PDAC were significantly associated with poor differentiation, maximum tumor size >5 cm, invasion, regional lymph node metastasis, and TNM III/IV disease (P<0.05). In PDAC, Jagged1 expression positively correlated with DLL4 expression. Univariate Kaplan-Meier analysis showed that positive Jagged1 and DLL4 expressions were significantly associated with shorter survival in patients with PDAC. Multivariate Cox regression analysis showed that positive Jagged1 and DLL4 expressions were independent prognostic factors for poor prognosis of patients with PDAC. CONCLUSION: Positive Jagged1 and DLL4 expression is closely correlated with severe clinicopathological characteristics and poor prognosis in patients with PDAC.

A new phenylethanoid glycoside from Incarvillea compacta.

A new phenylethanoid glycoside, 3'''-O-methylcampneoside I (1), was isolated from the 90% ethanolic extract of the roots of Incarvillea compacta, together with three known compounds, campneoside I (2), ilicifolioside A (3), and campneoside II (4). Their structures were determined spectroscopically and compared with previously reported spectral data. Compound 1 existed as epimers and displayed better 1,1-diphenyl-2-picrylhydrazyl (DPPH)-free radical scavenging activity using di-tert-butyl-4-methylphenol (BHT) as the positive control. In addition, pretreatment of human HepG2 cells with compound 1 significantly increased the viability on CCl4-induced cell death.

The clinical significance of FRAT1 and ABCG2 expression in pancreatic ductal adenocarcinoma.

Pancreatic ductal adenocarcinoma (PDAC) is a highly malignant tumor with intrinsic resistance to cytotoxic agents. The molecular mechanisms associated with high malignancy and resistance to chemotherapy and radiotherapy have not been fully elucidated. This study investigated the clinicopathological significances of frequently rearranged in advanced T-cell lymphomas-1 (FRAT1) and ATP-binding cassette subfamily G member 2 (ABCG2) expression in PDAC. FRAT1 and ABCG2 protein expression in 106 PDAC, 35 peritumoral tissues, 55 benign pancreatic tissues, and 13 normal pancreatic tissues was measured by immunohistochemistry. FRAT1 and ABCG2 protein was overexpressed in PDAC tumors compared to peritumoral tissues, benign pancreatic tissues, and normal pancreatic tissues (P < 0.01). The percentage of cases with positive FRAT1 and ABCG2 overexpression was significantly higher in PDAC patients with poor differentiation, lymph node metastasis, invasion, and TNM stage III/IV disease than in patients with well-differentiated tumor, no lymph node metastasis and invasion, and TNM stage I/II disease (P < 0.05 or P < 0.01). In pancreatic tissues with benign lesions, tissues with positive FRAT1 and ABCG2 protein expression exhibited dysplasia or intraepithelial neoplasia. Kaplan-Meier survival analysis showed that PDAC patients with positive FRAT1 and ABCG2 expression survived significantly shorter than patients with negative FRAT1 and ABCG2 expression (P < 0.05 or P < 0.001). Cox multivariate analysis revealed that positive FRAT1 and ABCG2 expression was an independent poor prognosis factor in PDAC patients. FRAT1 and ABCG2 overexpression is associated with carcinogenesis, progression, and poor prognosis in patients with PDAC.