Additional file 6 of Utility of comprehensive genomic profiling in directing treatment and improving patient outcomes in advanced non-small cell lung cancer

Additional file 6. Study protocol and amendment records

Additional file 2 of Utility of comprehensive genomic profiling in directing treatment and improving patient outcomes in advanced non-small cell lung cancer

Additional file 2: Table S2. NGS panels and number of samples being tested

Additional file 1 of Utility of comprehensive genomic profiling in directing treatment and improving patient outcomes in advanced non-small cell lung cancer

Additional file 1: Table S1. List of associated clinical trials in the study

Predictive value of immunotherapy-induced inflammation indexes: dynamic changes in patients with nasopharyngeal carcinoma receiving immune checkpoint inhibitors

Immune checkpoint inhibitors (ICIs) have achieved substantial advancements in clinical care. However, there is no strong evidence for identified biomarkers of ICIs in NPC. In this retrospective study, 284 patients were enrolled into a training or validation cohort. Inflammatory indexes based on peripheral blood parameters were evaluated, including the systemic immune-inflammation index (SII), the neutrophil-lymphocyte ratio (NLR), the platelet-lymphocyte ratio (PLR), the lymphocyte-to-C-reactive protein ratio (LCR), and the lymphocyte-monocyte ratio (LMR). The optimum cut-off value for patient stratification was identified using X-tile. The Kaplan-Meier method and Cox’s proportional regression analyses were used to identify prognostic factors. Immunotherapy significantly changed the levels of SII, NLR, PLR, LCR and LMR in NPC patients. Patients with lower SII, NLR, and PLR, as well as those with higher LCR and LMR, before immunotherapy had superior PFS (all p p  Immune checkpoint inhibitor treatments significantly changed the levels of SII, NLR, PLR, LCR and LMR in NPC patients treated with immunotherapy. A lower baseline SII and a higher baseline LMR, and a reduction in SII and an elevation in LMR after immunotherapy are favorable factors for predicting survival among advanced NPC patients. There is no strong evidence for identified biomarkers of immune checkpoint inhibitors (ICIs) in nasopharyngeal carcinoma (NPC). Lower baseline SII and higher baseline LMR were related to better PFS. The dynamic changes of SII and LMR were independent prognostic factors for the survival of NPC patients receiving ICIs. Neutrophils, platelets, lymphocytes, and monocytes can be used as cheap and valuable biomarkers for predicting tumor response in NPC on immunotherapy.</p

Additional file 1 of Genomic and transcriptomic profiling of combined small-cell lung cancer through microdissection: unveiling the transformational pathway of mixed subtype

Additional file 1.. Table S1. Clinical details of cSCLC cases. Table S2. All somatic mutations of cSCLC samples. Table S3. Potential driver genes in cSCLC samples. Table S4. Other recurrently mutant genes in cSCLC samples. Table S5. Predicted neoantigens in cSCLC samples. Table S6. Somatic copy number variations in cSCLC samples. Table S7. Significant broad copy number variations in cSCLC samples. Table S8. Significant focal copy number variations in cSCLC samples. Table S9. CCF and clone clusters of somatic non-synonymous mutations in cSCLC samples. Table S10. clonality of somatic non-synonymous mutations in cSCLC samples. Table S11. Somatic evolutionary timings of mutations. Table S12. Immune cell fraction of cSCLC samples. Table S13. Immune-related pathways enrichment score of cSCLC samples

Additional file 4 of Utility of comprehensive genomic profiling in directing treatment and improving patient outcomes in advanced non-small cell lung cancer

Additional file 4: Figure S1. Stratified analysis in patients with different histologies who carried alterations with different actionability levels. A. Subgroup of lung adenocarcinoma: PFS and OS in patients carrying level 1-2 alterations treated with a matched therapy and a nonmatched therapy. B. Subgroup of lung adenocarcinoma: PFS and OS in patients carrying level 3-4 alterations treated with a matched therapy and a nonmatched therapy. C. Subgroup of other NSCLC histologies: PFS and OS in patients carrying level 1-2 alterations treated with a matched therapy and a nonmatched therapy. D. Subgroup of other NSCLC histologies: PFS and OS in patients carrying level 3-4 alterations treated with a matched therapy and a nonmatched therapy

Additional file 5 of Utility of comprehensive genomic profiling in directing treatment and improving patient outcomes in advanced non-small cell lung cancer

Additional file 5: Figure S2. Stratified analysis in patients with different timing of genomic profiling who carried alterations with different actionability levels. A. Treatment-naïve when genomically profiled: PFS and OS in patients carrying level 1-2 alterations treated with a matched therapy and a nonmatched therapy. B. Previously treated when genomically profiled: PFS and OS in patients carrying level 1-2 alterations treated with a matched therapy and a nonmatched therapy. C. Previously treated when genomically profiled: PFS and OS in patients carrying level 3-4 alterations treated with a matched therapy and a nonmatched therapy

Real-Time NMR-Based Drug Discovery to Identify Inhibitors against Fatty Acid Synthesis in Living Cancer Cells

Abnormal fatty acid metabolism is recognized as a key driver of tumor development and progression. Although numerous inhibitors have been developed to target this pathway, finding drugs with high specificity that do not disrupt normal cellular metabolism remains a formidable challenge. In this paper, we introduced a novel real-time NMR-based drug screening technique that operates within living cells. This technique provides a direct way to putatively identify molecular targets involved in specific metabolic processes, making it a powerful tool for cell-based drug screening. Using 2-13C acetate as a tracer, combined with 3D cell clusters and a bioreactor system, our approach enables real-time detection of inhibitors that target fatty acid metabolism within living cells. As a result, we successfully demonstrated the initial application of this method in the discovery of traditional Chinese medicines that specifically target fatty acid metabolism. Elucidating the mechanisms behind herbal medicines remains challenging due to the complex nature of their compounds and the presence of multiple targets. Remarkably, our findings demonstrate the significant inhibitory effect of P. cocos on fatty acid synthesis within cells, illustrating the potential of this approach in analyzing fatty acid metabolism events and identifying drug candidates that selectively inhibit fatty acid synthesis at the cellular level. Moreover, this systematic approach represents a valuable strategy for discovering the intricate effects of herbal medicine

Additional file 3 of Utility of comprehensive genomic profiling in directing treatment and improving patient outcomes in advanced non-small cell lung cancer

Additional file 3: Table S3. Baseline characteristics between patients carrying potentially actionable alterations treated with a matched (n = 440) and nonmatched therapy (n = 215)

Real-Time Observation of Conformational Changes and Translocation of Endogenous Cytochrome c within Intact Mitochondria

Cytochrome c (cyt c) is a multifunctional protein with varying conformations. However, the conformation of cyt c in its native environment, mitochondria, is still unclear. Here, we applied NMR spectroscopy to investigate the conformation and location of endogenous cyt c within intact mitochondria at natural isotopic abundance, mainly using widespread methyl groups as probes. By monitoring time-dependent chemical shift perturbations, we observed that most cyt c is located in the inner mitochondrial membrane and partially unfolded, which is distinct from its native conformation in solution. When suffering oxidative stress, cyt c underwent oxidative modifications due to increasing reactive oxygen species (ROS), weakening electrostatic interactions with the membrane, and gradually translocating into the inner membrane spaces of mitochondria. Meanwhile, the lethality of oxidatively modified cyt c to cells was reduced compared with normal cyt c. Our findings significantly improve the understanding of the molecular mechanisms underlying the regulation of ROS by cyt c in mitochondria. Moreover, it highlights the potential of NMR to monitor high-concentration molecules at a natural isotopic abundance within intact cells or organelles