Advances and challenges in the treatment of esophageal cancer

Esophageal cancer(EC)is one of the most common cancers with high morbidity and mortality rates.EC includes two histological subtypes,namely esophageal squamous cell carcinoma(ESCC)and esophageal adenocarcinoma(EAC).ESCC primarily occurs in East Asia,whereas EAC occurs in Western countries.The currently available treatment strategies for EC include surgery,chemotherapy,radiation therapy,molecular targeted therapy,and combinations thereof.However,the prognosis remains poor,and the overall five-year survival rate is very low.Therefore,achieving the goal of effective treatment remains challenging.In this review,we discuss the latest developments in chemotherapy and molecular targeted therapy for EC,and comprehensively analyze the application prospects and existing problems of immunotherapy.Collectively,this review aims to provide a better understanding of the currently available drugs through in-depth analysis,promote the development of new therapeutic agents,and eventually improve the treatment outcomes of patients with EC.

The novel ER stress inducer Sec C triggers apoptosis by sulfating ER cysteine residues and degrading YAP via ER stress in pancreatic cancer cells

Pancreatic adenocarcinoma(PAAD) is one of the most lethal malignancies. Although gemcitabine(GEM) is a standard treatment for PAAD, resistance limits its application and therapy. Secoemestrin C(Sec C) is a natural compound from the endophytic fungus Emericella, and its anticancer activity has not been investigated since it was isolated. Our research is the first to indicate that Sec C is a broad-spectrum anticancer agent and could exhibit potently similar anticancer activity both in GEM-resistant and GEM-sensitive PAAD cells. Interestingly, Sec C exerted a rapid growth-inhibiting effect(80% death at 6 h), which might be beneficial for patients who need rapid tumor shrinkage before surgery. Liquid chromatography/mass spectrometry and N-acetyl-L-cysteine(NAC) reverse assays show that Sec C sulfates cysteines to disrupt disulfide-bonds formation in endoplasmic reticulum(ER) proteins to cause protein misfolding, leading to ER stress and disorder of lipid biosynthesis. Microarray data and subsequent assays show that ER stress-mediated ER-associated degradation(ERAD) ubiquitinates anddownregulates YAP to enhance ER stress via destruction complex(YAP-Axin-GSK-βTr CP), which also elucidates a unique degrading style for YAP. Potent anticancer activity in GEM-resistant cells and low toxicity make Sec C a promising anti-PAAD candidate.

Solar cells sensitized by porphyrin dyes containing a substituted carbazole donor with synergistically extended absorption and suppressed the dye aggregation

To achieve high power conversion efficiency(PCE),three porphyrin sensitizers have been synthesized and explored to simultaneously enhance the photocurrent(JSC)and photovoltage(VOC).On basis of the XW4,a benzothiadiazole(BTD)unit has been introduced to afford XW57 with the aim to extend the absorption wavelength and enhance the light harvesting ability.As a result,a JSC of 13.72 mA/cm^2 has been obtained for XW57,higher than that of XW4.On this basis,XW58 has been prepared by modifying the carbazole-based donor with two bulky dihexyloxyphenyl groups,and the superior anti-aggregation character raises the VOC from 781 mV(XW4)to 844 mV.When both the BTD unit and the bulky groups are introduced to the acceptor and donor units,respectively,the resulting sensitizer XW59 exhibits a highest PCE value of 7.34%with synergistically enhanced JSC of 13.19 mA/cm^2 and VOC of 793 mV.These results provide further insight into developing high performance dye-sensitized solar cells.