Clinicopathological and prognostic value of lncRNA PANDAR expression in solid tumors: Evidence from a systematic review and meta-analysis

PANDAR (promoter of CDKN1A antisense DNA damage activated RNA) has been shown to be aberrantly expressed in many types of cancer. Considering conflicting data, the current study was aimed to assess its potential role as a prognostic marker in malignant tumors. A comprehensive literature search of PubMed, Medline, and Web of Science was performed to identify all eligible studies describing the use of PANDAR as a prognostic factor for different types of cancer. Data related to overall survival (OS) and clinicopathologic features were collected and analyzed. The pooled hazard ratio (HR) and odds radio (OR) with a 95% confidence interval (CI) were used to estimate associations. Ten original studies containing 1,231 patients were included. The results showed that in patients with cancer, high PANDAR expression is correlated with lymph node metastasis (LNM; OR = 2.57; 95% CI, 1.76–3.81; p < 0.001), tumor stage (OR = 2.90; 95% CI, 1.25–6.75; p = 0.013), and tumor size (OR = 1.79; 95% CI, 1.11–2.91; p = 0.018). However, sensitivity analysis further demonstrated a significant association between high PANDAR expression and OS, both in multivariate and univariate analysis models (pooled HR 2.01; 95% CI, 1.17–3.44 and pooled HR 2.62; 95% CI, 1.98–3.47, respectively), after omitting one study. These results suggested that PANDAR expression might be indicative of advanced disease and poor prognosis in patients with cancer. Further studies are necessary to determine the value of this risk stratification biomarker in clinical management of patients with cancer.     

Further development of local IL-2 therapy of cancer: multiple versus single IL-2 treatment of transplanted murine colon carcinoma

We have compared the effect of one and up to four local IL-2 treatments of transplanted MC38 colon carcinoma. A single IL-2 treatment prolonged the survival time (p=0.015), but no cure was obtained. One local IL-2 treatment inhibited tumor growth for about 1 week. After the start of tumor regrowth, a further IL-2 injection was given. After four IL-2 injections 6 out of 13 mice were cured. Histological studies show that IL-2 induced a local vascular leakage syndrome leading to massive peritumoral edema and subsequent necrosis of tumor tissue. IL-2 also attracted infiltrating cells, mainly macrophages. Subsequent IL-2 injections led to complete tumor regression. We believe that the combination of necrotic tumor debris and the IL-2–induced macrophage reaction enhanced a tumor-specific immune response. This local IL-2 application was not toxic.     

The presence of a galanin-like peptide in the gut neuroendocrine system of Lampetra fluviatilis and Acipenser transmontanus: an immunohistochemical study

Galanin is a brain-gut neuropeptide present in the central and peripheral nervous systems of vertebrates. In the present survey, the galaninergic and the diffuse endocrine systems of the alimentary canal of the river lamprey, Lampetra fluviatilis, and the white sturgeon, Acipenser transmontanus, were studied by immunohistochemistry. The results show the presence of galanin-like immunoreactive endocrine cells in the gut of L. fluviatilis. In addition, a galanin-like immunoreactivity was detected in enteric intramural neurons of both species. It is conceivable that the galaninergic system plays in both species a role in the regulation of the gut muscle contractility and in the modulation of mucosal secretive/absorptive processes. In A. transmontanus, the presence of galanin-like immunoreactive nerve fibres associated with components of the gut associated-lymphoid tissue is possibly correlated with a control of the defensive events at this site. The presence of a galanin-like immunoreactivity in the neuroendocrine system of these two ancient fishes confirms the hypothesis on the early occurrence of this regulative molecule in the gastro-enteric system of vertebrates.     

R-Type Ca<Superscript>2+</Superscript>-channel Activity Is Associated with Chromogranin A Secretion in Human Neuroendocrine Tumor BON Cells

This electrophysiological study was undertaken to investigate the role of voltage-operated Ca(2+) channels (VOCCs) in cultivated human neuroendocrine tumor (NET) cells. Patch-clamp techniques, measurements of intracellular Ca(2+) ([Ca(2+)](i)), and secretion analysis were performed using cultured human NET BON cells. Ba(2+) inward currents through R-type channels (Ca(V)2.3) were measured and identified by SNX-482 (10 n M), a novel voltage-sensitive R-type Ca(2+) channel antagonist. In the presence of nifedipine (5 micro M), omega-Conotoxin GVIA (100 n M) and omega-Agatoxin IVA (20 n M), R-type channel currents were also detectable. Release of Ca(2+) from intracellular Ca(2+) stores by intracellular application of inositol-1,4,5-trisphosphate (InsP(3); 10 micro M) via the patch pipette during whole-cell configuration as well as induction of capacitative Ca(2+) entry (CCE), a passive maneuver to release Ca(2+) from intracellular Ca(2+) stores, led to an increase in [Ca(2+)](i). This effect could be reduced by SNX-482 (20 n M). In addition, SNX-482 (25 n M) also decreased chromogranin A (CgA) secretion, whereas omega-Conotoxin GVIA (500 n M) and nifedipine (5 micro M) failed to reduce CgA secretion. We conclude that these data reveal neuronal R-type channel activity (Ca(V)2.3), for the first time associated with CgA secretion in BON cells. Influx of Ca(2+) by activation of R-type channels may lead to an increase of intracellular Ca(2+), which stimulates CgA secretion. Thus, R-type channels could play an important role in certain clinical characteristics of NETs, such as the hypersecretion syndrome.     

The STC-1 cells express functional orexin-A receptors coupled to CCK release

Orexins are newly discovered neuropeptides regulating feeding and vigilance and have been detected in neuroendocrine cells of the gut. Potential neuroendocrine functions of orexin are unknown. Therefore, the effects of orexin-A on the intestinal neuroendocrine cell line, STC-1, were investigated as a model system. RT-PCR demonstrated the presence of both OX(1) and OX(2) receptors. Stimulation with orexin-A produced a dose-dependent release of cholecystokinin (CCK), which was abolished by removal of extracellular Ca(2+) or the presence of the voltage-gated L-type Ca(2+)-channel blocker diltiazem (10 microM). Orexin-A (Ox-A) elevated intracellular Ca(2+), which was dependent on extracellular Ca(2+). Furthermore, orexin-A caused a membrane depolarization in the STC-1 cells. Ox-A neither elevated cAMP levels nor stimulated phosphoinositide turnover in these cells. These data demonstrate a functional orexin receptor in the STC-1 cell line. Ox-A produces CCK release in these cells, by a mechanism involving membrane depolarization and subsequently activation of L-type voltage-gated Ca(2+)-channels.     

Reactivity of peptidyl-tyrosine to hydroxylation and cross-linking

Tyrosine residues of neuroendocrine peptides are frequently the targets of oxidation reactions, one of which involves hydroxylation to peptidyl-3, 4-dihydroxy-phenyl-L-alanine (DOPA). The reactivity in vitro of peptidyl-DOPA in two neuroendocrine peptides, a neurotensin fragment (pELYENK) and proctolin (RYLPT), was investigated using ultraviolet-visible scanning spectrophotometry and matrix-assisted laser desorption ionization mass spectrometry following oxidation by tyrosinase and periodate. The peptides form covalently coupled dimers and trimers, and their masses are consistent with the presence of diDOPA cross-links. Lysine does not appear to participate in multimer formation because it is efficiently recovered in fragmentation ladders using subtilisin. While multimer formation in the neurotensin-derived peptide can be blocked effectively by adding N-acetyl-DOPA-ethylester to the reaction medium, the DOPA ethylester couples itself four to five times to each peptide.     

区域效应－一个前列腺癌早期诊断的新思路

目前临床上有许多怀疑前列腺癌但穿刺阴性的病例,为了避免漏诊,多数患者必须接受重复穿刺。尽管部分患者经重复穿刺确诊为前列腺癌,而更多患者经过长期随访以及反复穿刺最终确诊为良性病变。近期研究证实,癌灶附近的组织学表现正常的组织中也可发生与癌灶相似的分子改变。因此,我们认为在前列腺癌的发生过程中存在区域效应。在这一理论指导下,选择适当的可反映前列腺癌区域效应的标记物,在穿刺阴性的标本中检出与癌灶相似的分子改变,就可以帮助临床医生在常规病理诊断之前,提前预测前列腺癌的发生。如果能够找到这样的标记物,并在大规模的诊断试验中证实其可行性,那么就可以极大地改善前列腺癌诊断的现状。     

Wnt/β-catenin signaling regulates cancer stem cells in lung cancer A549 cells

Wnt/β-catenin signaling plays an important role not only in cancer, but also in cancer stem cells. In this study, we found that β-catenin and OCT-4 was highly expressed in cisplatin (DDP) selected A549 cells. Stimulating A549 cells with lithium chloride (LiCl) resulted in accumulation of β-catenin and up-regulation of a typical Wnt target gene cyclin D1. This stimulation also significantly enhanced proliferation, clone formation, migration and drug resistance abilities in A549 cells. Moreover, the up-regulation of OCT-4, a stem cell marker, was observed through real-time PCR and Western blotting. In a reverse approach, we inhibited Wnt signaling by knocking down the expression of β-catenin using RNA interference technology. This inhibition resulted in down-regulation of the Wnt target gene cyclin D1 as well as the proliferation, clone formation, migration and drug resistance abilities. Meanwhile, the expression of OCT-4 was reduced after the inhibition of Wnt/β-catenin signaling. Taken together, our study provides strong evidence that canonical Wnt signaling plays an important role in lung cancer stem cell properties, and it also regulates OCT-4, a lung cancer stem cell marker.