Clinical significance of neutrophil gelatinase-associated lipocalin and sdLDL-C for coronary artery disease in patients with type 2 diabetes mellitus aged ≥ 65 years.

BACKGROUND AND AIMS: Although type 2 diabetes mellitus (T2DM) and coronary artery disease (CAD) share many common pathological and physiological characteristics, there are few studies assessing the predictive capacity of novel biomarkers in occurrence and development of CAD in T2DM patients aged ≥ 65 years. In addition, T2DM patients aged ≥ 65 years are prone to CAD. Therefore, it is of great significance to find novel biomarkers for the development CAD in T2DM. METHODS: In this retrospective cohort study, 579 T2DM patients aged ≥ 65 years were consecutively enrolled in this work, and 177 of whom had major adverse cardiovascular and cerebrovascular events (MACCE: cardiovascular or cerebrovascular death, acute coronary syndrome, coronary stent implantation, and stroke) during the follow up. Univariate and multivariate factors were employed to analyze the correlation between each variable and the occurrence of MACCE, and the Spearman's rank correlation analysis was performed to assess the relationships between Neutrophil gelatinase-associated lipocalin (NGAL) and small dense low-density lipoprotein-cholesterol (LDL-C) (sdLDL-C). The receiver operating characteristic (ROC) curve was adopted to determine the predictive value of NGAL and sdLDL-C elevation for MACCE in T2DM patients aged ≥ 65 years. RESULTS: After a median 48 months follow-up [19, (10 ~ 32) ], the levels of NGAL, sdLDL-C, hemoglobin A1c (HbA1c), LDL-C, and apolipoprotein B (ApoB) were significantly higher while those of high-density lipoprotein cholesterol (HDL-C) and apolipoprotein A I (ApoA-I) were lower in MACCE positive group. NGAL correlated to body mass index (BMI) (r = 0.391, P = 0.001) and triglyceride (TG) (r = 0.228, P = 0.032), and high-sensitivity CRP (hsCRP) (r = 0.251, P = 0.007), and neutrophils (r = 0.454, P = 0.001), sdlDL-C level was found to be positively correlated with LDL-C (r = 0.413, P = 0.001), TG (r = 0.432, P = 0.001), and ApoB (r = 0.232, P = 0.002); and it was negatively correlated with HDL-C (r = -0.362, P = 0.031) and ApoA-I (r = -0.402, P = 0.001). Age-adjusted Cox regression analysis showed that NGAL (HR = 1.006, 95% confidence interval (CI): 1.005-1.008, P < 0.001) and sdLDL-C (HR = 1.052, 95% CI: 1.037-1.066, P < 0.001) were independently associated with occurrence of MACCE. ROC curve analysis showed that NGAL (area under ROC (AUC) = 0.79, 95% CI: 0.75-0.84, P < 0.001) and sdlDL-C (AUC = 0.76, 95% CI: 0.72-0.80, P < 0.001) could predict the occurrence of MACCE (area under ROC. NGAL combined with sdlDL-C could predict the occurrence of MACCE well (AUC = 0.87, 95% CI: 0.84-0.90, P < 0.001). CONCLUSION: The higher NGAL and sdLDL-C in T2DM patients aged ≥ 65 years were significantly and independently associated with the risk of MACCE, and showed higher clinical values than other lipid biomarkers or other chronic inflammation, so they were expected to be the most effective predictors of MACCE assessment.

The role of hypoxic mesenchymal stem cells in tumor immunity.

The emerging evidence has shown that mesenchymal stem cells (MSCs) not only exert a significant role in the occurrence and development of tumors, but also have immunosuppressive potential in tumor immunity. Hypoxia is a sign of solid tumors, but how functions of hypoxic MSCs alter in the tumor microenvironment (TME) remains less well and comprehensively described. Herein, we mostly describe and investigate recent advances in our comprehension of the emerging effects of different tissue derived MSCs in hypoxia condition on tumor progression and development, as well as bidirectional influence between hypoxic MSCs and immune cells of the TME. Furthermore, we also discuss the potential drug-resistant and therapeutic role of hypoxic MSCs. It can be envisaged that novel and profound insights into the functionality of hypoxic MSCs and the underlying mechanisms in tumor and tumor immunity will promote the meaningful and promising treatment strategies against tumor.

Plasma CXCL3 Levels Are Associated with Tumor Progression and an Unfavorable Colorectal Cancer Prognosis.

Background: The CXC chemokines belong to a unique family of chemotactic cytokines that influence the initiation, progression, and clinical outcome of many tumor types. Herein, we investigated the association of the CXC-chemokine ligand 3 (CXCL3) with tumor progression and an unfavorable prognosis for colorectal cancer (CRC). Methods: The quantitative real-time polymerase chain reaction was used to explore the expression of CXCL3 in CRC tissue, adjacent tissue, and plasma. The usefulness of plasma levels of CXCL3 for the diagnosis of CRC was evaluated by receiver operating characteristic curve analysis. Pearson's correlation analysis assessed relationships among plasma CXCL3, cancer tissue CXCL3, and plasma carcinoembryonic antigen (CEA). Kaplan-Meier analysis was used to assess the survival of CRC patients with high and low expression levels of CXCL3. Survival differences were compared by log-rank test. Results: Initial analysis of the GSE156720 dataset identified CXCL3 as the most enriched CXCL gene in CRC patients. Higher CXCL3 levels were detected in CRC tissue than in adjacent tissue (P < 0.001). Compared to healthy controls, CRC patient plasma CXCL3 levels were higher (P < 0.001). The area under the curve was 0.81 with a sensitivity of 0.71 and specificity of 0.82, distinguishing CRC from other tumor types. Plasma CXCL3 was positively related to CXCL3 in cancer tissue (r = 0.78, P < 0.01), and also to plasma CEA (r = 0.50, P < 0.01). Plasma CXCL3 was also related to tumor size (P = 0.034), staging (P < 0.001), tumor stage (P = 0.003), differentiation (P = 0.001), and lymph node metastasis (P = 0.007), but not to sex (P = 0.853), age (P = 0.691), tumor site (P = 1.347), or distant metastasis (P = 1.218). Conclusions: CXCL3 levels were increased in CRC patients, with plasma CXCL3 levels associated with tumor progression and an unfavorable CRC prognosis. The results of this study suggest that plasma CXCL3 may be a novel diagnostic and prognostic biomarker for CRC.

Exposure Optimization Trial for Patients With Medical Implants During MRI Exposure: Balance Between the Completeness and Efficiency.

Elongated conductors, such as pacemaker leads, can couple to the MRI radio-frequency (RF) field during MRI scan and cause dangerous tissue heating. By selecting proper RF exposure conditions, the RF-induced power deposition can be suppressed. As the RF-induced power deposition is a complex function of multiple clinical factors, the problem remains how to perform the exposure selection in a comprehensive and efficient way. The purpose of this work is to demonstrate an exposure optimization trail that allows a comprehensive optimization in an efficient and traceable manner. The proposed workflow is demonstrated with a generic 40 cm long cardio pacemaker, major components of the clinical factors are decoupled from the redundant data set using principle component analysis, the optimized exposure condition can not only reduce the in vivo power deposition but also maintain good image quality.

SPC24 Regulates breast cancer progression by PI3K/AKT signaling.

Breast cancer is a heterogeneous disease, presenting as several diverse clinical and histologic varieties and it is now the most frequently diagnosed cancer and is the sixth leading cause of cancer-related death in Chinese women. SPC24 is an important component of the mitotic checkpoint machinery and its carcinogenic roles have been shown in several cancers, including anaplastic thyroid cancer, hepatocellular carcinoma, and osteosarcoma. However, the role of SPC24 in breast cancer is still unclear. Here, we show SPC24 is highly expressed in breast cancer compared with the normal tissues. In addition, we observe that SPC24 knockdown can lead to attenuated cell growth, increased cell apoptosis and cell cycle progression. Consistent with the breast cancer cell results, the in vivo growth of the SPC24-knocking down cells was significantly inhibited. Interestingly, molecular analysis indicates that SPC24 regulates PI3K/AKT kinase pathway, indicating the important of SPC24 for clinical treatment. In aggregate, our results provide an oncogenic functionality of SPC24 in breast cancer progression.

Oleanolic Acid Inhibits Colorectal Cancer Angiogenesis by Blocking the VEGFR2 Signaling Pathway.

BACKGROUND: Angiogenesis is a crucial process that regulated by multiple intracellular signaling pathways including MEK/ERK and JNK/SAPK. Thus, many inhibitors have developed to these pathways as anti-cancer therapeutic strategies. Oleanolic acid (OA) is a natural pentacyclic triterpenoic acid compound that present in various herbal medicines. It has been used as antitumor agent for various cancers including colorectal cancer (CRC), which attenuates angiogenesis. OBJECTIVE: To study the molecular mechanism of OA suppressing angiogenesis. METHOD: The proliferation of human umbilical vein endothelial cells (HUVECs) was determined by MTT and the invasion and migration of them were measured by wound-healing Assay, transwell migration assay and tube formation assay. The xenograft mouse model was used to study the effect of OA blocking angiogenesis in vivo. The Western blot was used to checked the phosphorylation of VEGFR2. RESULTS: OA attenuates HUVECs invasion, migration, tube formation and vascular sprouting. Moreover, OA suppresses HUVECs sprout and tube formation. Importantly, OA also blocks angiogenesis in HUVECs and colorectal cancer cells (HCT-116) both in vitro and in vivo. OA-dependent suppression of tumor angiogenesis mediated by blocking the phosphorylation of the vascular endothelial growth factor receptor-2 (VEGFR2) that results in inhibition of MEK/ERK/JNK pathway. CONCLUSION: Our results suggest that inhibition of tumor angiogenesis via the suppression VEGFR2 phosphorylation may be one of the underlying mechanisms by which OA exerts its anti-cancer effect.

A potential prognostic biomarker SPC24 promotes tumorigenesis and metastasis in lung cancer.

RESULTS: SPC24 is over-expressed in clinical lung adenocarcinoma samples, and high level of SPC24 is associated with advanced stages of lung tumors. Knocking down SPC24 repressed cell growth and promoted apoptosis. SPC24 deficiency reduced cancer cell migration as well. E-cadherin, one of the epithelial-mesenchymal transition markers, was up-regulated in the knockdown cells, along with down-regulation of N-cadherin and Vimentin. Oncomine expression analyses further confirmed that high level of SPC24 is associated with tumors from smokers, recurrent patients, or patients with shorter survivals. PURPOSE AND METHODS: To reveal the role of SPC24, an important component of kinetochore, in the tumorigenesis of lung cancer, we performed Oncomine and immunohistochemistry (IHC) analyses for SPC24 in human lung adenocarcinoma tumors. We knocked down SPC24 in two non-small cell lung cancer (NSCLC) cell lines, PC9 and A549, by siRNA and evaluated cell proliferation, apoptosis, and migration in the SPC24-deficient cells. Using a mouse xenograft model, we compared in vivo tumor growth of the knockdown and control cells. We further performed multiple Oncomine expression analyses for SPC24 in various lung cancer datasets with important clinical characteristics and risk factors, including survival, recurrence, and smoking status. CONCLUSIONS: SPC24 is a novel oncogene of lung cancer, and can serve as a promising prognostic biomarker to differentiate lung tumors that have various clinicopathological characteristics. The findings of the current study will benefit the diagnosis, management, and targeted therapy of lung cancer.

Meta-analysis of association between rs1447295 polymorphism and prostate cancer susceptibility.

AIMS: A number of studies have found that the single nucleotide polymorphisms (SNPs) within the 8q24 region of genome were associated with the susceptibility of prostate cancer. Association between 8q24 SNP variant rs1447295 and higher risk of prostate cancer had been investigated, but those studies were incomplete and the conclusions were obscure. METHODS: To better elucidate the relationship between rs1447295 polymorphism and the susceptibility of prostate cancer, we performed a more comprehensive meta-analysis about the association between rs1447295 polymorphism and prostate cancer susceptibility by collecting relevant articles published up to November, 2016 and excluding many replicated cohort data existing in previous reports, which made the conclusion more reliant and objective. RESULTS: The results showed that there was a significant prostate cancer risk associated with rs1447295 polymorphism not only in the total groups, but also in American, European and Asian descent subgroups. Meanwhile, a comprehensive analysis about the association between rs1447295 polymorphism and prostate cancer risk were conducted by using different clinical characteristic stratifications including Gleason score, tumor stage and PSA level. The result showed that rs1447295 polymorphism was correlated with different stages of prostate cancer. CONCLUSIONS: There are strong association between rs1447295 polymorphism and prostate cancer susceptibility in different ethnic groups and different prostate cancer stage, suggesting that rs1447295 might serve as a reliable biomarker for prostate cancer diagnosis.

Systematic identification of key genes and pathways in the development of invasive cervical cancer.

BACKGROUND: Cervical cancer progresses through different stages: a long stage of precancerous lesions, then high-grade squamous intraepithelial lesion (HSIL) stage in which precancerous lesions transform into invasive cervical carcinoma, and finally invasive squamous cell carcinomas (SCC) which is difficult to be treated and can be deadly. METHODS AND RESULTS: To identify critical genes for the development and progression of cervical cancer development, we analyzed an online database comprised of normal squamous cervical epithelia samples, HSIL samples and SCC of cervix. Dysregulated genes were identified in both early stage (from normal to HSIL stage) and late stage (from HSIL stage to SCC stage) of cervical cancer. By overlapping these dysregulated genes, we found that three genes, including CDKN2A, IL1R2 and RFC4, were not only changed in HSIL, but also significantly changed in SCC, indicating that their dysregulation may contribute to cervical cancer development. Several altered pathways during tumor progression were also discovered, including those involved in cell proliferation, cell cycle and cell division. CONCLUSIONS: Our findings suggest that dysregulations of CDKN2A, IL1R2 and RFC4 may contribute to cervical cancer progression and they might be potential diagnostic markers and therapeutic drug targets.

The effect and clinical efficacy of lienal polypeptide injection combined with FOLFOX chemotherapy regimen in colon cancer patients.

The aim was to investigate the clinical efficacy and immunomodulatory effect of lienal polypeptide injection combined with postoperative FOLFOX chemotherapy regimen in colon cancer patients. A total of 84 colon cancer patients were selected between January, 2014 and December, 2015. The selected patients were randomly divided into the observation (42 patients) and control (42 patients) groups. The observation group patients were treated with FOLFOX chemotherapy regimen combined with lienal polypeptide, whereas, the control group patients were treated with FOLFOX chemotherapeutic regimen only. After two cycles of treatment, Karnofsky performance scale (KPS) index, side effects or toxicity and the peripheral blood T-cell subset analyses in the two groups of patients were evaluated. The patients who received FOLFOX chemotherapeutic regimen combined with lienal polypeptide in the observation group showed significantly higher score of KPS than patients of the control group (P<0.05). No significant difference in the spectrum of side effects such as nausea, vomiting, neurotoxicity, liver and kidney dysfunction, oral mucosal inflammation were observed in the treatment groups. However, the incidence of bone marrow suppression was significantly lower in the observation group in comparison with the control group (P<0.05). Additionally, the CD8+ T cells were decreased in the observation group patients compared to the control group, while the ratio of CD4+ T/CD8+ T (TH/TC) cells and the number of natural killer cells were higher in the observation group patients than the control group (P<0.05). In conclusion, the results suggest that, when the standard FOLFOX chemotheraputic regimen is combined with lienal polypeptide to treat colon cancer, it enhances the general well being of patients and strengthens the immune system in the combat against cancer.