Effect of the proton pump inhibitors (PPIs) lansoprazole, omeprazole and pantoprazole at three different concentrations on the MICs of tigecycline in clinical isolates of 6 species of pathogens.

a<p>The number of strains of each species tested in the study.</p><p>Increased MICs in >50% of isolates are indicated in boldface.</p

Time–kill curves showing effects of proton pump inhibitors (PPIs) on the activity of tigecycline.

<p>MIC_T, MIC for tigecycline alone; MIC_L5 and MIC_L50, MIC for tigecycline in combination with 5 mg/L and 50 mg/L lansoprazole; MIC_A5 and MIC_A50, MIC for tigecycline in combination with 5 mg/L and 50 mg/L omeprazole; MIC_P5 and MIC_P50, MIC for tigecycline in combination with 5 mg/L and 50 mg/L pantoprazole. •, Control; ▴, 50 mg/L lansoprazole; ▾, 50 mg/L omeprazole; ▪, 50 mg/L pantoprazole; Δ, 5 mg/L lansoprazole; ▽, 5 mg/L omeprazole; □, 5 mg/L pantoprazole; ○, tigecycline alone. The <i>in vitro</i> time-kill experiments were duplicated; mean values are plotted. In all duplicate experiments, similar time-kill results were obtained.</p

Cathepsin B‑Activated PET Tracer for <i>In Vivo</i> Tumor Imaging

Cathepsin B, a lysosomal protease, is considered as a crucial biomarker for tumor diagnosis and treatment as it is overexpressed in numerous cancers. A stimulus-responsive SF scaffold has been reported to detect the activity of a variety of tumor-associated enzymes. In this work, a small-molecule PET tracer ([68Ga]­NOTA-SF-CV) was developed by combining an SF scaffold with a cathepsin B-specific recognition substrate Cit-Val. Upon activation by cathepsin B, [68Ga]­NOTA-SF-CV could form the cyclization product in a reduction environment, resulting in reduced hydrophilicity. This unique property could effectively prevent exocytosis of the tracer in cathepsin B-overexpressing tumor cells, leading to prolonged retention and amplified PET imaging signal. Moreover, [68Ga]­NOTA-SF-CV had great targeting specificity to cathepsin B. In vivo microPET imaging results showed that [68Ga]­NOTA-SF-CV was able to effectively visualize the expression level of cathepsin B in various tumors. Hence, [68Ga]­NOTA-SF-CV may be served as a potential tracer for diagnosing cathepsin B-related diseases

Multifunctional Probe Based on “Chemical Antibody–Aptamer” for Noninvasive Detection of PD-L1 Expression in Cancer

Immune checkpoint inhibitors (ICIs) therapy based on programmed cell death ligand 1 (PD-L1) has shown significant development in treating several carcinomas, but not all patients respond to this therapy due to the heterogeneity of PD-L1 expression. The sensitive and accurate quantitative analysis of in vivo PD-L1 expression is critical for treatment decisions and monitoring therapy. In the present study, an aptamer-based dual-modality positron emission tomography/near-infrared fluorescence (PET/NIRF) imaging probe was developed, and its specificity and sensitivity to PD-L1 were assessed in vitro and in vivo. The probe precursor NOTA-Cy5-R1 was prepared by using automated solid-phase oligonucleotide synthesis. PET/NIRF dual-modality probe [68Ga]Ga-NOTA-Cy5-R1 was successfully synthesized and radiolabeled. The binding specificity of [68Ga]Ga-NOTA-Cy5-R1 to PD-L1 was evaluated by flow cytometry, fluorescence imaging, and cellular uptake in A375-hPD-L1 and A375 cells, and it showed good fluorescence properties and stability in vitro. In vivo PET/NIRF imaging studies illustrated that [68Ga]Ga-NOTA-Cy5-R1 can sensitively and specifically bind to PD-L1 positive tumors. Meanwhile, the rapid clearance of probes from nontarget tissues achieved a high signal-to-noise ratio. In addition, changes of PD-L1 expression in NCI-H1299 xenografts treated with cisplatin (CDDP) were sensitivity monitored by [68Ga]Ga-NOTA-Cy5-R1 PET imaging, and ex vivo autoradiography and western blot analyses correlated well with the change of PD-L1 expression in vivo. Overall, [68Ga]Ga-NOTA-Cy5-R1 showed notable potency as a dual-modality PET/NIRF imaging probe for visualizing tumors and monitoring the dynamic changes of PD-L1 expression, which can help to direct and promote the clinical practice of ICIs therapy

Supplementary Figure 3 from Myeloid Differentiation Factor 88 Promotes Growth and Metastasis of Human Hepatocellular Carcinoma

PDF File - 868K, MyD88 regulated the expression of several tumor modifiers in HCC-LM3 cells. And inhibition of PI3K/Akt, p38 and MEK-ERK pathway decreased NF-�B signal activities upregulated by overexpressing MyD88 in HCC-LM3 as analyzed by the luciferase activities.</p

Supplementary Figure 4 from Myeloid Differentiation Factor 88 Promotes Growth and Metastasis of Human Hepatocellular Carcinoma

PDF File - 656K, Inhibition of MEK-ERK pathway reduced promotion of MyD88 in the migration of HCC cells. And inhibition of IL-6 also reduced promotion of MyD88 in the migration of HCC cells, but not in one's proliferation.</p

Supplementary Figure Legends from Myeloid Differentiation Factor 88 Promotes Growth and Metastasis of Human Hepatocellular Carcinoma

PDF File - 145K, Legends for Supplementary Figures 1-5</p

Supplementary Figure 5 from Myeloid Differentiation Factor 88 Promotes Growth and Metastasis of Human Hepatocellular Carcinoma

PDF File - 444K, HCC cells expressed low level of TLRs (Toll-like receptors) and relative high level IL-1R compared with that in normal liver cell line HL7702. And alterations in the Ras pathway in HCC cells showed that Ras pathway and MyD88 expression is not related in HCC cells.</p

Supplementary Figure 1 from Myeloid Differentiation Factor 88 Promotes Growth and Metastasis of Human Hepatocellular Carcinoma

PDF File - 4550K, Photographs of immunostaining of MyD88 and CD68 in serial sections from HCC tissue samples were taken for further analyses.</p

Supplementary Tables 1-5 from Myeloid Differentiation Factor 88 Promotes Growth and Metastasis of Human Hepatocellular Carcinoma

The clinicopathologic characteristics of 110 cases of HCC, relationship between MyD88 expression and survival rate, Lenti-Virus shMyD88 inhibit tumorigenesis and metastasis of MHCC-PDF File - 194K, LM3 cells in nude mice, primers used in this study and antibodies used in this study.</p