Purpose: Pancreatic cancer is a highly aggressive malignant tumour with poor prognosis. The median survival is only 6 months. This study investigated the prognostic value of nuclear export protein chromosomal region maintenance/exportin 1/Xpo1 (CRM1) expression in pancreas cancer. Methods: CRM1 expression was detected, by Western blot, in pancreatic tissue from 69 cancer patients and 10 normal subjects. Results: CRM1 showed increased expression in pancreatic cancer tissue (P = 0.007). The high expression of CRM1 was associated with increased serum levels of CEA (P = 0.002) and CA19-9 (P = 0.005). There was an association between CRM1 expression and tumour size (P = 0.01), lymphadenopathy (P = 0.004) and liver metastasis (P = 0.003). High CRM1 expression was not correlated with the other clinicopathological parameters. High CRM1 expression was a prognostic indicator for progression-free survival (PFS) (P = 0.006) as well as overall survival (OS) (P = 0.001). Expression of CRM1 was an independent prognostic parameter for poorer PFS and OS (95% CI, 1.27–5.39). Conclusions: CRM1 expression demonstrated prognostic value in pancreatic cancer. Prospective studies are required to determine the prognostic role of high expression of CRM1 in pancreatic cancer.
Qin and co-workers use photocatalytic conditions to generate a nitrogencentered radical from aniline-type sulfonamide, which reverses the conventional reactivity between two electron-donating amine and enamine groups and initiates radical cascade reactions with excellent chemo-, regio-, and diastereoselectivity. The power of this distinct method has been demonstrated by the efficient syntheses of 33 monoterpenoid indole alkaloids belonging to four families.
Hypoxia can increase the resistance of tumor cells to radiotherapy and chemotherapy. However, the dense extracellular matrix, high interstitial fluid pressure, and irregular blood supply often serve as physical barriers to inhibit penetration of drugs or nanodrugs across tumor blood microvessels into hypoxic regions. Therefore, it is of great significance and highly desirable to improve the efficiency of hypoxia-targeted therapy. In this work, living photosynthetic bacteria (PSB) are utilized as hypoxia-targeted carriers for hypoxic tumor therapy due to their near-infrared (NIR) chemotaxis and their physiological characteristics as facultative aerobes. More interestingly, we discovered that PSB can serve as a kind of photothermal agent to generate heat through nonradiative relaxation pathways due to their strong photoabsorption in the NIR region. Therefore, PSB integrate the properties of hypoxia targeting and photothermal therapeutic agents in an “all-in-one” manner, and no postmodification is needed to achieve hypoxia-targeted cancer therapy. Moreover, as natural bacteria, noncytotoxic PSB were found to enhance immune response that induced the infiltration of cytotoxicity T lymphocyte. Our results indicate PSB specifically accumulate in hypoxic tumor regions, and they show a high efficiency in the elimination of cancer cells. This proof of concept may provide a smart therapeutic system in the field of hypoxia-targeted photothermal therapeutic platforms.
The asymmetric total syntheses of a group of structurally complex Kopsia alkaloids, (-)-kopsine, (-)-isokopsine, (+)-methyl chanofruticosinate, (-)-fruticosine, and (-)-kopsanone, has been achieved. The key strategies for the construction of the molecular complexity in the targets included an asymmetric Tsuji-Trost rearrangement to set the first quaternary carbon center at C20, an intramolecular cyclopropanation by diazo decomposition to install the second and third quaternary carbon centers at C2 and C7, respectively, and a SmI -promoted acyloin condensation to assemble the isokopsine core. A radical decarboxylation of an isokopsine-type intermediate results in a thermodynamic partial rearrangement to give N-decarbomethoxyisokopsine and N-decarbomethoxykopsine, two key intermediates for the syntheses of Kopsia alkaloids with different subtype core structures.
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