Breakthrough therapy for peritoneal carcinomatosis of gastric cancer:Intraperitoneal chemotherapy with taxanes

The effect of chemotherapy on peritoneal carcinomatosis(PC) of gastric cancer remains unclear.Recently,the intraperitoneal(IP) administration of taxanes [e.g.,paclitaxel(PTX) and docetaxel(DOC)] during the perioperative period has shown promising results.Herein,we summarized the rationale and methodology for using IP chemotherapy with taxanes and reviewed the clinical results.IP administered taxanes remain in the IP space at an extremely high concentration for 48-72 h.The drug directly infiltrates peritoneal metastatic nodules from the surface and then produces antitumor effects,making it ideal for IP chemotherapy.There are two types of perioperative IP chemotherapy with taxanes: neoadjuvant intraperitoneal and systemic chemotherapy and sequential perioperative intraperitoneal chemotherapy(SPIC).In SPIC,patients receive neoadjuvant IP chemotherapy and the same regimen of IP chemotherapy after cytoreductive surgery(CRS) until disease progression.Usually,a taxane dissolved in 500-1000 m L of saline at ordinary temperature is administered through an IP access port on an outpatient basis.According to phase Ⅰ?studies,the recommended doses(RD) are as follows: IP DOC,45-60 mg/m2; IP PTX [without intravenous(IV) PTX],80 mg/m2; and IP PTX(with IV PTX),20 mg/m2.Phase Ⅱ studies have reported a median survival time of 14.4-24.6 mo with a 1-year overall survival of 67%-78%.A phase Ⅲ study comparing S-1 in combination with IP and IV PTX to S-1 with IV cisplatin started in 2011.The prognosis of patients who underwent CRS was better than that of those who did not; however,this was partly due to selection bias.Although several phase Ⅱ studies have shown promising results,a randomized controlled study is needed to validate the effectiveness of IP chemotherapy with taxanes for PC of gastric cancer.

Molecules with a TEMPO-based head group as high-performance organic friction modifiers

High-performance organic friction modifiers(OFMs)added to lubricating oils are crucial for reducing energy loss and carbon footprint.To establish a new class of OFMs,we measured the friction and wear properties of N-(2,2,6,6-tetramethyl-1-oxyl-4-piperidinyl)dodecaneamide referred to as C12Amide-TEMPO.The effect of its head group chemistry,which is characterized by a rigid six-membered ring sandwiched by an amide group and a terminal free oxygen radical,was also investigated with both experiments and quantum mechanical(QM)calculations.The measurement results show that C12Amide-TEMPO outperforms the conventional OFMs of glyceryl monooleate(GMO)and stearic acid,particularly for load-carrying capacity,wear reduction,and stability of friction over time.The friction and wear reduction effect of C12Amide-TEMPO is also greatly superior to those of C12Ester-TEMPO and C12Amino-TEMPO,in which ester and amino groups replace the amide group,highlighting the critical role of the amide group.The QM calculation results suggest that,in contrast to C12Ester-TEMPO,C12Amino-TEMPO,and the conventional OFMs of GMO and stearic acid,C12Amide-TEMPO can form effective boundary films on iron oxide surfaces with a unique double-layer structure:a strong surface adsorption layer owing to the chemical interactions of the amide oxygen and free radical with iron oxide surfaces,and an upper layer owing to the interlayer hydrogen-bonding between the amide hydrogen and free radical or between the amide hydrogen and oxygen.Moreover,the intralayer hydrogen-bonding in each of the two layers is also possible.We suggest that in addition to strong surface adsorption,the interlayer and intralayer hydrogen-bonding also increases the strength of the boundary films by enhancing the cohesion strength,thereby resulting in the high tribological performance of C12Amide-TEMPO.The findings in this study are expected to provide new hints for the optimal molecular design of OFMs.