Search

Recent advances are achieved in the design and development of efficient organic photosensitizers (PSs), especially with fluorescence imaging navigation in the second near‐infrared (NIR‐II, 1000–1700 nm) region. However, there are simply a handful of NIR‐II emissive organic PSs with efficient oxygen‐independent capability due to the scarcity of high‐performance NIR‐responsive organic materials and targeted delivery. Herein, a NIR‐II‐emissive organic nanomedicine with biomimetic engineering for high‐performance NIR‐II imaging and targeted multiple phototherapies of pancreatic tumors is reported. An A‐D‐A‐type conjugated small‐molecule TPC is designed and used to prepare water‐dispersive nanoparticles, which demonstrated high efficiency for type I and type II photodynamic performances, good photothermal conversion of 57%, and bright NIR‐II emission with a quantum yield of 9.8% under 808 nm light irradiation. With pancreatic cancer cell membrane camouflage, the biomimetic TPC nanomedicine achieved high‐resolution and targeted bioimaging of whole‐body blood vessels and tumors. Antitumor experiments demonstrated the high efficiency of the biomimetic TPC nanomedicine for pancreatic tumor elimination and good biosafety with 808 nm light irradiation. This work demonstrated a NIR‐II‐emissive versatile nanomedicine with enhanced tumor‐targeting for high‐resolution NIR‐II bioimaging and superior phototheranostics, providing a feasible idea for the evolution of targeted and high‐performance theranostics. [ABSTRACT FROM AUTHOR]

Background: Umbelliprenin is a sesquiterpene coumarin isolated from Artemisia absinthium L. and shows antitumor effects in various cancers by inducing apoptosis. However, the antitumor effect of umbelliprenin in human pancreatic cancer has not been clarified. Methods: The antitumor effects were determined by MTT and AnnexinV/PI double staining assay in vitro and xenograft mice in vivo. Autophagy was determined via immunofluorescence analysis. Apoptotic or autophagic related proteins were measured by immunoblotting. The pancreatic cancer cell stemness were determined by mammosphere formation and ALDEFLUOR assay. Results: It revealed that umbelliprenin inhibited pancreatic cancer cell proliferation in vitro and pancreatic cancer tumor growth in vivo. Moreover, umbelliprenin induced pancreatic cancer cell BxPC3 apoptosis and autophagy as evidenced by upregulated apoptosis and autophagy‐ related protein expression (p < 0.01). Blocking autophagy by 3‐MA or Atg7 knockout enhanced umbelliprenin‐induced apoptosis (p < 0.05). Umbelliprenin also reduced pancreatic cancer cell stemness by reducing Oct4, Nanog, and Sox2 mRNA levels (p < 0.01). Mechanistically, umbelliprenin greatly inhibited Akt/mTOR and Notch1 signal pathway. Conclusion: Umbelliprenin may be a novel therapeutic approach for pancreatic cancer treatment. [ABSTRACT FROM AUTHOR]

In this population-based retrospective study, we aimed to investigate the association between age at diagnosis and prognosis of pancreatic cancer (PC) patients using data from the National Cancer Institute's Surveillance, Epidemiology, and the End Results database. Different factors for stratification, like race, sex, year of diagnosis, pathological grade, American Joint Committee on Cancer stage, historic stage, and tumour location, were included to compare the survival rates of patients of different age groups, and the five-year survival rate was calculated. Multivariate analysis using Cox regression was performed to control for confounder bias, and the hazard ratio was calculated. In total, 126,066 patients were enrolled in this study. The five-year PC-specific survival of patients aged 20–40 years was almost three times that of patients aged >40 years. Stratified by race, sex, year of diagnosis, pathological grade, clinical stage, and tumour location, a descending trend of survival was observed with an increase in age. On multivariate analysis, the mortality risk of PC patients aged 40–80 years was twice that of patients aged <40 years; however, patients aged >80 years had a mortality risk three times that of patients aged <40 years. The survival rate of PC patients has improved in the last few decades. Age at diagnosis is a significant and negative prognostic factor for PC, and patients diagnosed at a relatively earlier stage had the best survival. [ABSTRACT FROM AUTHOR]

Abstract Ethnopharmacological relevance Radix Scutellariae (RS) , the dried root of Scutellariae baicalensis Georgi, known as a herbal medicine in several Asian countries including China, has been widely used to treat inflammation, hypertension, cardiovascular disease as well as cancer. The total flavonoid aglycone extracted (TFAE) was extracted by ethyl acetate and this extraction methodology was optimized and obtained the protection of Chinese patents. Aim of the study To investigate the underlying mechanism of the chemotherapeutic effects of TFAE in inducing autophagy and apoptosis in pancreatic cancer cells in vitro and in vivo. Materials and methods We performed CCK8 assays, AnnexinV-FITC/PI staining, flow cytometry assays, transmission electron microscopy, immunofluorescence analysis and Western blot to study the molecular mechanism of TFAE in inducing autophagy and apoptosis in pancreatic cancer cells in vitro and in vivo. Results In vitro , TFAE exhibits significant anti-tumor activity against pancreatic cancer cell lines, especially for BxPC3 (IC 50 = 6.5 μg mL−1). Moreover, TFAE induces apoptosis and autophagy as evidenced by the increased apoptosis or autophagy-related protein level, the increased the fraction of apoptotic cells and the punctuate patterns of LC3 II. Furthermore, TFAE induce autophagy through PI3K/Akt/mTOR inhibition. Interestingly, pharmacological block autophagy by 3-MA enhanced TFAE-induced apoptosis, indicating that TFAE induced autophagy functions as a cytoprotective process against apoptosis. In vivo , 150 mg/kg TFAE inhibited the BxPC3 tumor growth in immune deficient mice with the inhibitory rate of 66.87% and induced both apoptosis and autophagy. Conclusion TFAE have anti-tumor activity against pancreatic cancer and can induce apoptosis and autophagy through PI3K/Akt/mTOR signal pathway. TFAE might be a potential anticancer drug to be further developed for human pancreatic cancer therapy. Graphical abstract fx1 [ABSTRACT FROM AUTHOR]

Despite the importance of metabolic reprogramming in cancer cells, the molecular mechanism regulating the tumor metabolic shift is still poorly understood. Deregulation of Jumonji-C domain-containing protein 5 (JMJD5) has been associated with multiple facets of biological processes in cancer cells. However, the role of JMJD5 in pancreatic cancer cells has seldom been discussed and requires further investigation. In the present study, by silencing or overexpressing JMJD5 in pancreatic cancer cells, we examined the impact of JMJD5 on cell proliferation and glucose metabolism. Using a dual luciferase assay, we assessed the effect of JMJD5 on the transcriptional activity of the c-Myc target gene. Analyzing The Cancer Genome Atlas and the Gene Expression Omnibus datasets revealed that low JMJD5 expression was associated with poor prognosis in patients with pancreatic cancer. JMJD5 loss promoted pancreatic cancer cell proliferation and induced a cellular metabolic shift from oxidative phosphorylation to glycolysis. In addition, in vivo experiments confirmed that ectopic JMJD5 expression inhibited cancer cell growth and the expression of glycolytic enzymes, such as lactate dehydrogenase and phosphoglycerate kinase 1. Moreover, JMJD5 negatively regulated c-Myc expression, the main regulator of cancer metabolism, leading to decreased c-Myc-targeted gene expression. Overall, the present study indicated that decreased JMJD5 expression promoted cell proliferation and glycolytic metabolism in pancreatic cancer cells in a c-Myc-dependent manner. • JMJD5 is positively correlated with pancreatic cancer patient survival. • JMJD5 negatively regulates the cell proliferation and glucose metabolism in pancreatic cancer cells. • JMJD5 regulates glucose metabolism in a c-Myc-dependent manner. [ABSTRACT FROM AUTHOR]