Optical Spectrsocopy of Murine breast tumor to distinguish indolent from aggressive disease

Breast cancer accounts for 30% of all cancer. Metastasis is the primary cause of death among breast cancer patients. Additionally, current molecular profiling methods such as Oncotype DX, which are expensive and not widely available at all clinical facilities, only determine the risk of recurrence after treatment. Therefore, there are no current method capable of identifying metastatic patients in advance.As a result, there is an unmet clinical need to develop a cost-effective prognostic to differentiate between indolent and aggressive breast tumors. In this study, we implemented diffuse reflectance spectroscopy (DRS) system to evaluate functional changes in tumor xenografts originated from four breast cancer cell lines with variable metastatic potential. The murine mammary cell lines 4T1, 4T07, 168FARN, and 67NR were injected into the flanks of mice to grow tumor xenografts. In addition, we used CRISPR/Cas-9 to delete TWIST- a gene known to promote tumor metastasis - and generate an indolent version of 4T1 (4T1-TWIST KO) that was also grown as xenografts. We collected optical data from these tumors bearing animals and using a look-up table inverse model, we determined vascular oxygen saturation (SO2), total hemoglobin concentration (cHb), and tissue light scattering at four different tumor volumes. Our preliminary data shows functional differences between indolent and aggressive tumors that can be further investigated in human cell line and patient-derived tumors

Longitudinal Monitoring of Tumor Response to Immune Checkpoint Inhibitors using Diffuse Optical Spectroscopy

Immune checkpoint drugs have completely changed the way people treat metastatic melanoma and non-small-cell lung cancer. While the impacts of these immunological checkpoints and their suppression on T cell function are well characterized, their consequences on the tumor microenvironment are not. In a CT26 mouse colorectal cancer model, we employed diffuse reflectance spectroscopy to track in vivo tumor microenvironmental alterations in response to immune checkpoint inhibitors. On three separate days, animals bearing CT26 tumor xenografts were given anti-PD-L1, anti-CTLA-4, a combination of both inhibitors, and isotype control. Within the first 6 days, monotherapy with either anti-PD-L1 or anti-CTLA-4 resulted in a significant increase in tumor vascular oxygenation. The combination of increased oxygenated hemoglobin and decreased deoxygenated hemoglobin caused reoxygenation in anti-CTLA-4-treated tumors, indicating a probable alteration in tumor oxygen consumption following treatment. Reoxygenation was predominantly owing to a rise in oxygenated hemoglobin within a minor change in deoxygenated hemoglobin in anti-PD-L1-treated tumors, indicating a potential increase in tumor perfusion. Except for tumors treated with both inhibitors in combination, none of the other tumor groups demonstrated any reduction in tumor volume. Following therapy, there were no significant changes in tumor oxygenation in the combination treatment group. These results show that diffuse reflectance spectroscopy may detect changes in the tumor microenvironment after immunotherapy and that such non-invasive approaches can be used to predict early tumor response to immune checkpoint inhibitor

Phosphoproteomics data classify hematological cancer cell lines according to tumor type and sensitivity to kinase inhibitors

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Unbiased mm-wave Line Surveys of TW Hya and V4046 Sgr: The Enhanced C2H and CN Abundances of Evolved Protoplanetary Disks

We have conducted the first comprehensive mm-wave molecular emission line surveys of the evolved circumstellar disks orbiting the nearby T Tauri stars TW Hya and V4046 Sgr AB. Both disks are known to retain significant residual gaseous components, despite the advanced ages of their host stars. Our unbiased broad-band radio spectral surveys of the TW Hya and V4046 Sgr disks were performed with the Atacama Pathfinder Experiment (APEX) 12 meter telescope and are intended to yield a complete census of bright molecular emission lines in the range 275-357 GHz (1.1-0.85 mm). We find that lines of 12CO, 13CO, HCN, CN, and C2H, all of which lie in the higher-frequency range, constitute the strongest molecular emission from both disks in the spectral region surveyed. The molecule C2H is detected here for the first time in both disks, as is CS in the TW Hya disk. The survey results also include the first measurements of the full suite of hyperfine transitions of CN N=3-2 and C2H N=4-3 in both disks. Modeling of these CN and C2H hyperfine complexes in the spectrum of TW Hya indicates that the emission from both species is optically thick and may originate from very cold disk regions. It furthermore appears that the fractional abundances of CN and C2H are significantly enhanced in these evolved protoplanetary disks relative to the fractional abundances of the same molecules in the environments of deeply embedded protostars.Comment: 29 pages, 6 figures; to appear in Vol. 791 of The Astrophysical Journa