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Background Systemic chemotherapy is often the last resort of advanced cutaneous T-cell lymphoma (CTCL). Tumor recurrence and adverse effects of systemic chemotherapy are the main limitations. Objective We aim to investigate the metabolic alterations in tumor cells after CHOP (cyclophosphamide, hydroxydaunorubicin, oncovin and prednisone) chemotherapy. Methods and results In advanced CTCL, CHOP chemotherapy has no survival benefit and the duration of response is significantly inferior to other canonical treatments. HIF-1α is significantly elevated in lesions of advanced MF patients as well as tumor cell line Hut78 and tumor xenograft mice model. CHOP therapy also increased glycolytic activities in a HIF-1α-dependent manner. In CTCL xenograft tumor mice model, lesional cells showed a significant increase in IL-17F after chemotherapy, shifting toward a Th17 phenotype, which process is also regulated by HIF-1α. Echinomycin, HIF-1α inhibitor, was co-administered in xenograft tumor mouse models with CHOP and showed a significant reduction in tumor growth. Conclusion CHOP chemotherapy promotes glycolysis and IL-17 pathways in a HIF-1α-dependent fashion. Furthermore, HIF-1α blockade is promising as an accompanying agent in systemic chemotherapy for patients with advanced CTCL.

Cutaneous T-cell lymphoma (CTCL) is a heterogeneous group of skin-homing T-cell neoplasms. Clinical management is stage based but diagnosis and prognosis could be extremely challenging. The presented study aims to explore the metabolic profiling of CTCL by an accelerated untargeted metabolomics data analysis tool "Mummichog" to facilitate the discoveries of potential biomarkers for clinical early stage diagnosis, prognosis, and treatments in CTCL. Ultra high-performance liquid chromatography-quadrupole time-of-flight-based untargeted metabolomics were conducted on the skin and plasma of CTCL mice. It showed that the metabolism of skin changed greatly versus control samples in the development of CTCL. Increased l-glutamate and decreased adenosine monophosphate were the most essential metabolic features of CTCL tumor and tumor adjacent skins. Unique metabolism changes in tumor adjacent non-involved skin tissues (ANIT) occurred in the progress of carcinogenesis, including upregulated cytidine-5'-triphosphate, aberrant biosynthesis of prostaglandins, pyrimidine, mevalonate pathway, and tryptophan degradation. Sharply elevated 5-phospho-α-d-ribose 1-diphosphate (PRPP) marked the final state of tumor in CTCL. In the plasma, systematic shifts in corticosterone, sphingolipid, and ceramide metabolism were found. These uncovered aberrant metabolites and metabolic pathways suggested that the metabolic reprogramming of PRPP in tumor tissues may cause the disturbance of cytidine and uridine metabolic homeostasis in ANIT. Accumulative cytidine-5'-triphosphate in ANIT may exert positive feedback on the PRPP level and leads to CTCL further development. In addition, the accelerated data analysis tool "Mummichog" showed good practicability and can be widely used in high-resolution liquid chromatography mass spectrometry-based untargeted metabolomics.

Thermal proteome profiling is a powerful energetic-based chemical proteomics method to reveal the ligand-protein interaction. However, the costly multiplexed isotopic labeling reagent, mainly Multiplexed isobaric tandem mass tag (TMT), and the long mass spectrometric time limits the wide application of this method. Here a simple and cost-effective strategy by using dimethyl labeling technique instead of TMT labeling is reported to quantify proteins and by using the peptides derived from the same protein to determine significantly changed proteins in one LC-MS run. This method is validated by identifying the known targets of methotrexate and geldanamycin. In addition, several potential off-targets involved in detoxification of reactive oxygen species pathway are also discovered for geldanamycin. This method is further applied to map the interactome of adenosine triphosphate (ATP) in the 293T cell lysate by using ATP analogue, adenylyl imidodiphosphate (AMP-PNP), as the ligand. As a result, a total of 123 AMP-PNP-sensitive proteins are found, of which 59 proteins are stabilized by AMP-PNP. Approximately 53% and 20% of these stabilized candidate protein targets are known as ATP and RNA binding proteins. Overall, above results demonstrated that this approach could be a valuable platform for the unbiased target proteins identification with reduced reagent cost and mass spectrometric time.

In this work, the effects of surface ligands of cadmium selenide (CdSe) nanocrystals on energetic disorder and charge transport of poly (3-hexylthiophene-2,5-diyl):cadmium selenide (P3HT:CdSe) hybrid bulk heterojunction solar cells were studied. Photo-induced current transient spectroscopy (PICTS) was employed to quantitatively characterize the trap state energies in P3HT:CdSe hybrid solar cells from pyridine (Py) and tert-butylthiol (tBT) treated CdSe nanocrystals. A data processing workflow to extract the trap emission spectra was implemented in the form of solving an inverse problem with regularization techniques. We observed significant differences in the trap state distribution in P3HT:CdSe(tBT) compared to P3HT:CdSe(Py) solar cells, and we found that devices based on P3HT:CdSe(Py) had deeper level trap states. Additionally, transient photoconductivity measurements were performed on P3HT:CdSe solar cells for the purpose of examining the effects of ligands on charge transport. The results were self-consistent with PICTS analysis in that P3HT:CdSe(tBT) devices exhibited a greater than three-fold enhancement in carrier mobility relative to P3HT:CdSe(Py) devices, which we attributed to a decreased depth of trap states.