1α,25(OH)2D3 Analog, MART-10, Inhibits Neuroendocrine Tumor Cell Metastasis After VEGF-A Stimulation.

AIMS: Pancreatic neuroendocrine tumors (PanNETs) are usually diagnosed in an advanced stage. Most patients with PanNETs die of metastasis. Vascular endothelial growth factor-A (VEGF-A) is a strong stimulator of angiogenesis and tumor metastasis. We aimed to investigate the effect of MART-10 [19-nor-2α-(3-hydroxypropyl)-1α,25(OH)2D3], a 1α,25-dihydroxy-vitamin D3 (1α,25(OH)2D3) analog, on PanNET cell metastasis after VEGF-A stimulation. MATERIALS AND METHODS: Migration and invasion assays, western blot, and immunofluorescent staining were applied in this study. RESULTS: VEGF-A increased PanNET cell migration and invasion, which was attenuated by 1α,25(OH)2D3 and MART-10. VEGF-A treatment stimulated epithelial-mesenchymal transition (EMT) of PanNET cells. During this process, expression of snail family transcriptional repressor 1 and 2, and fibronectin was up-regulated. 1α,25(OH)2D3 and MART-10 counteracted VEGF-A-induced EMT. In addition, expression of neuropilin 1, a key protein in VEGF-A signaling, was down-regulated by 1α,25(OH)2D3 and MART-10. Furthermore, synthesis of F-actin was increased by VEGF-A and reduced by 1α,25(OH)2D3 and MART-10. CONCLUSION: Our data indicate that MART-10 could be deemed a promising drug for PanNET treatment.

Transient Elastography for Spleen Stiffness Measurement in Patients With Cirrhosis: Role in Degree of Thrombocytopenia.

OBJECTIVES: The purpose of our study was to evaluate the relationship between spleen stiffness measured by transient elastography and the degree of thrombocytopenia in patients with liver cirrhosis. METHODS: A total of 67 patients with liver cirrhosis were prospectively enrolled in the study. All patients underwent single-day hematologic and biochemical tests, sonography, and transient elastography of the liver and spleen. Thrombocytopenia was categorized as mild (platelet count, 75,000-150,000/µL), moderate (50,000-75,000/µL), and severe (<50,000/µL). RESULTS: The degree of thrombocytopenia was significantly correlated with spleen stiffness (P = .001) and spleen size (P = .002) but not with liver stiffness (P = .086). In patients without splenomegaly, spleen stiffness values were significantly higher in patients with thrombocytopenia than in those without thrombocytopenia (P = .035). In patients with splenomegaly, spleen stiffness values were significantly higher in patients with moderate to severe thrombocytopenia than in those with a normal platelet count or mild thrombocytopenia (P = .007). Compared to liver stiffness, spleen stiffness showed a better and statistically significant correlation with platelet count and spleen size in patients with cirrhosis. CONCLUSIONS: The degree of thrombocytopenia was directly correlated with spleen stiffness, irrespective of the presence of splenomegaly. The clinical phenomenon of unexpected thrombocytopenia may be explained by a subtle or irreversible change in spleen stiffness.

1α,25(OH)2D3 Analog, MART-10, Inhibits Neuroendocrine Tumor Cell Growth Through Induction of G0/G1 Cell-cycle Arrest and Apoptosis.

BACKGROUND: Neuroendocrine tumors (NETs) are the second most common digestive malignancy. For advanced NETs, survival is not satisfactory. Vitamin D has emerged as a promising anticancer drug. MATERIALS AND METHODS: Cell proliferation assay, western blot, flow cytometry, and terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) assays were applied. RESULTS: We demonstrated that RIN-m cells, neuroendocrine tumor cells, expressed vitamin D receptor (VDR) and VDR expression increased with increasing exposure to 1α,25-dihydroxyvitamin D3 [1α,25(OH)2D3] or MART-10, a 1α,25(OH)2D3 analog. MART-10 had anti-growth effect on RIN-m cells comparable to those of 1α,25(OH)2D3 The growth inhibition of both drugs was mediated by induction of cell-cycle arrest at G0/G1 phase and apoptosis. Western blot assay further revealed that this G0/G1 arrest was due to the up-regulation of p27 and down-regulation of cyclin dependent kinase 4 (CDK4), with MART-10 also reducing CDK6. Apoptosis induction was further supported by increased cleaved caspase-3 expression after treatment. CONCLUSION: MART-10 appears to be a promising regimen for NET treatment.

Carbon dioxide insufflation during colonoscopy can significantly decrease post-interventional abdominal discomfort in deeply sedated patients: A prospective, randomized, double-blinded, controlled trial.

BACKGROUND AND AIM: CO2 has been reported to be absorbed from the bowel more rapidly than air, resulting in a discomfort reduction after colonoscopy. Its role in deeply sedated patients is limited. This study was designed to investigate the efficacy and safety of CO2 insufflation during colonoscopy in patients deeply sedated with propofol. METHODS: A total of 125 continuous patients were randomly assigned to receive either CO2 (n = 63) or air (n = 62) insufflation during propofol-sedated colonoscopy. Postcolonoscopy abdominal pain, distention, and satisfaction were assessed at 1, 3, and 24 h after the procedure, and the proportions of pain-free and distention-free patients were compared. Residual bowel gas in the colon and small bowel was evaluated at 1 h after colonoscopy. End-tidal CO2 and O2 saturation was measured for safety analysis. RESULTS: There was a significant difference between the two groups regarding the postcolonoscopy abdominal pain, distention, and subjective satisfaction at 1 h (P < 0.001) and 3 h (P < 0.01) after the procedure. Patients' pain and distention at 1 and 3 h after the procedure were significantly lower in the CO2 group (P < 0.01). Residual bowel gas in the colon and small bowel was significantly less in the CO2 group (P < 0.001). There was no significant difference in end-tidal CO2 levels between two groups before, during, and after the procedure. CONCLUSIONS: Compared with air, CO2 insufflation during colonoscopy reduced postcolonoscopy abdominal discomfort and improved patients' satisfaction. It was safe to use CO2 insufflation in deeply sedated colonoscopy.

Label-free detection of protein-protein interactions using a calmodulin-modified nanowire transistor.

In this study, we describe a highly sensitive and reusable silicon nanowire field-effect transistor for the detection of protein-protein interactions. This reusable device was made possible by the reversible association of glutathione S-transferase-tagged calmodulin with a glutathione modified transistor. The calmodulin-modified transistor exhibited selective electrical responses to Ca2+ (> or = 1 microM) and purified cardiac troponin I (approximately 7 nM); the change in conductivity displayed a linear dependence on the concentration of troponin I in a range from 10 nM to 1 microM. These results are consistent with the previously reported concentration range in which the dissociation constant for the troponin I-calmodulin complex was determined. The minimum concentration of Ca2+ required to activate calmodulin was determined to be 1 microM. We have also successfully demonstrated that the N-type Ca2+ channels, expressed by cultured 293T cells, can be recognized specifically by the calmodulin-modified nanowire transistor. This sensitive nanowire transistor can serve as a high-throughput biosensor and can also substitute for immunoprecipitation methods used in the identification of interacting proteins.

Multi-port polarization-independent optical quasi-circulators by using a pair of holographic spatial- and polarization- modules.

In this paper we proposed an alternative type of multi-port polarization-independent optical quasi-circulator by using a pair of holographic spatial- and polarization- modules. The prototype is fabricated and experimentally tested. In addition, the operating principles, the characteristics and the performances of this device are discussed. The merits of this design include polarization-independence, compactness, high isolation, low polarization mode dispersion, and easy fabrication. Furthermore, the number of ports can be scaled up easily.

Improved N-port optical quasi-circulator by using a pair of orthogonal holographic spatial- and polarization- modules.

Based on the flexibilities of light beam propagation in three dimensions, we propose an improved N-port optical quasi-circulator by using a pair of orthogonal holographic spatial- and polarization- modules. All optical elements are located in parallel planes that are perpendicular to the optical axis. The number of optical elements is decreased, and a higher performance optical quasi-circulator without crosstalk and polarization mode dispersion can be easily achieved. A prototype of 5-port polarizationindependent optical quasi-circulator operating at a wavelength of 1300nm was assembled and tested to show its validities.