Application of tumoroids derived from advanced colorectal cancer patients to predict individual response to chemotherapy.

Therapeutic approaches of advanced colorectal cancer are more complex, here we present a living biobank of patient-derived tumoroids from advanced colorectal cancer patients and show examples of how these tumoroids can be used to to simulate cancer behavior ex vivo and provide more evidence for tumoroids could be utilized as a predictive platform during chemotherapy treatment to identify the chemotherapy response. Morphological, histological and genomic characterization analysis of colorectal cancer tumoroids was conducted. Further, we treated colorectal cancer tumoroids with different drugs to detect cellular activities to evaluate drug sensitivity using CellTiter-Glo 3 D cell viability assay. Then the drug sensitivity of tumoroids was compared with clinical outcomes. Our results implied that tumoroids recapitulated the histological features of the original tumours and genotypic profiling of tumoroids showed a high-level of similarity to the matched primary tumours. Dose-response curves, area under the curve and tumour inhibitory rate of each therapeutic profiling calculations in tumoroids demonstrated a great diversity and we gained 88.24% match ratio between the sensitivity data of tumoroids with their paired patients' clinical outcomes. tumour inhibitory rate of each treatment parameters in tumoroids performed positive correlation with progression-free survival while area under the curve of each treatment parameters performed negative correlation with progression-free survival of the corresponding patients. In summary, We presented a living biobank of tumoroids from advanced colorectal cancer patients and show tumoroids got great potential for predicting clinical responses to chemotherapy treatment of advanced colorectal cancer.

FGF-2 suppresses neuronal autophagy by regulating the PI3K/Akt pathway in subarachnoid hemorrhage.

The degree of early brain injury (EBI) is a significant factor that affects the prognosis of patients with subarachnoid hemorrhage (SAH). Evidence has shown that fibroblast growth factor-2 (FGF-2) may alleviate the serious consequences of EBI after SAH. The objective of the current study was to investigate the underlying mechanism that mediates the neuroprotective effects of FGF-2 in the SAH rat model. Sprague-Dawley (SD) rats that underwent different treatments were divided into various groups. FGF-2 was administered intranasally to rats in the treatment group within 30 min after modeling. Rapamycin (an autophagy activator) or LY294002 (a PI3K/Akt pathway inhibitor) was administered intracerebroventricularly (i.c.v.) 30 min before modeling. Neurological scale and brain water content were measured in the brain tissue of the rats. TUNEL staining, Western blot, and immunofluorescence staining were performed to examine and compare the diverse effects of FGF-2 treatment, activated autophagy, and inhibited the PI3K/Akt pathway. We found that FGF-2 treatment effectively reduced the number of TUNEL-positive cells, decreased the brain water content, and improved the neurological function of rats after SAH. Additionally, the expression levels of autophagy-related proteins (LC3 and Beclin-1) were obviously decreased in the FGF-2 treatment group compared with the SAH + vehicle group. The therapeutic effects of FGF-2 in the SAH + FGF-2+rapamycin group were weakened compared with that in the SAH + FGF-2+DMSO group. In the event of the PI3K/Akt pathway inhibition, the expression levels of LC3 and Beclin-1 were enhanced, and the therapeutic effects of FGF-2 were compromised. In summary, our data collectively demonstrated that FGF-2 may suppress autophagy levels to play a neuroprotective role, at least partially by activating the PI3K/Akt pathway. These results highlight FGF-2 as a promising solution to the clinical intervention of SAH.