Cisplatin is a chemotherapeutic drug commonly used in clinics. However, acquired resistance confines its application in chemotherapeutics. To overcome the acquired resistance to cisplatin, it is reasoned, based on our previous findings of mediation of cellular responses by [Gd@C 82 (OH) 22 ] n nanoparticles, that [Gd@C 82 (OH) 22 ] n may reverse tumor resistance to cisplatin by reactivating the impaired endocytosis of cisplatin-resistant human prostate cancer (CP-r) cells. Here we report that exposure of the CP-r PC-3-luc cells to cisplatin in the presence of nontoxic [Gd@C 82 (OH) 22 ] n not only decreased the number of surviving CP-r cells but also inhibited growth of the CP-r tumors in athymic nude mice as measured by both optical and MRI. Labeling the CP-r PC-3 cells with transferrin, an endocytotic marker, demonstrated that pretreatment of the CPr PC-3-luc cells with [Gd@C 82 (OH) 22 ] n enhanced intracellular accumulation of cisplatin and formation of cisplatin-DNA adducts by restoring the defective endocytosis of the CP-r cancer cells. The results suggest that [Gd@C 82 (OH) 22 ] n nanoparticles overcome tumor resistance to cisplatin by increasing its intracellular accumulation through the mechanism of restoring defective endocytosis. The technology can be extended to other challenges related to multidrug resistance often found in cancer treatments.A s a major chemotherapeutic agent for tumor treatment, cisplatin remains a cornerstone of the present-day chemotherapy regimens against not only epithelial malignancies but also a number of metastatic and advanced malignancies (1, 2). However, because of high toxicity and easy development of drug resistance, successful treatment with cisplatin often is limited (3,4). Following the discovery of ATP-binding cassette (ABC) transporters and their roles in drug resistance in various types of tumors (5), much research has been done to explore the relationship between ABC transporter activity and specific chemotherapeutics, including cisplatin. Because no ABC transporter has been identified for "pumping" cisplatin out of cisplatin-resistant human prostate cancer (CP-r) cells (6-8), it would be difficult to sensitize CP-r cells by using any known strategy that targets resistant cancer cells by inhibiting multidrug resistance (MDR)-associated proteins on plasma membrane of the CP-r cells. Diffusion has been considered as a pathway for cisplatin to penetrate plasma membrane. Recently, studies have indicated that cisplatin entered cells by endocytosis and other mechanisms (9-12).To increase susceptibility of cancer cells to cisplatin, i.e., to reverse drug resistance, many efforts have been made through chemical modification, gene therapy, vector delivery, and other means (2, 9, 13). Combination of traditional chemotherapy with nanotechnology may provide a promising alternative for novel cancer treatments. The use of nanoparticles to sensitize tumor cells to cisplatin in vitro and in vivo has been described recently (14-16). In these studies, cisplatin-encap...

Serine/arginine-rich (SR) proteins are a family of important splicing factors, which are involved in multiple aspects of RNA processing, including splicing, mRNA nuclear export, mRNA stability and translation. Previous studies have identified a number of SR proteins that exhibit abnormal expression in various tumor types. In the present study, the expression and function of serine/arginine-rich splicing factor 7 (SRSF7) were investigated in colon and lung cancer. Using tissue immunohistochemistry, it was observed that SRSF7 was overexpressed in colon and lung cancer tissues. As the role of SRSF7 in cancer remains to be fully elucidated, the expression of SRSF7 was knocked down in the present study by transfecting SRSF7-specific small interfering RNAs (siRNAs) into the HCT116 colon cancer cell line and A549 lung cancer cell line, which exhibited elevated expression of SRSF7. MTS assays, western blot analysis, flow cytometry and spectrofluorometer analyses were performed to assess the effects of SRSF7 knockdown on the proliferation and apoptosis of cells. The results demonstrated that the expression of SRSF7 was efficiently knocked down by SRSF7 siRNA, and that SRSF7 knockdown inhibited proliferation and enhanced apoptosis of HCT116 and A549 cells. Further experiments involving BEAS-2B cells stably overexpressing SRSF7, and A549 cells with stable knockdown of SRSF7 revealed that SRSF7 regulated the splicing of the apoptosis regulator Fas. Collectively, these data indicated that SRSF7 is critical for the survival of colon and lung cancer cells, and may be a potential therapeutic target for the treatment of colon and lung cancer.

Lithium–sulfur (Li–S) batteries are promising energy storage systems owing to their high theoretical energy density and low costs due to the abundant reserves of sulfur.

Cisplatin is one of the commonly-used chemotherapeutic drugs to efficiently treat malignant tumors in clinic, however, the adverse effects of cisplatin such as nephrotoxicity, neurotoxcity, and hemolytic uremic syndrome are often observed at its clinical doses (~60 mg/m 2 ), which limit its broader application. In earlier studies, little attention was paid to the subtle changes in the architecture of lymphatic organs after low doses of cisplatin treatment. This paper reviews current understanding of cisplatin-induced erythrocyte injury, and presents our latest finding that a low dose of cisplatin (3.6 mg/m 2 /day, 14 days) could induce specific hemosiderin deposition in spleen of both normal and hepatoma-22 (H22) inoculated Balb/C mice. This dose of cisplatin significantly inhibited H22-induced acute ascites development. No significant toxicity was induced by this dose of cisplatin to tissues except for hemosiderin accumulation in the spleen of both normal and H22 tumor-bearing mice. Increased splenic iron content and erythrocyte injury were observed after treatment with the low dose of cisplatin. The mRNA levels of ferroportin (FPN1) and ferritin were upregulated by 25 and 5-fold in spleen, respectively. Overexpression of FPN1 and ferritin protein were also been observed at protein levels by Western blotting analysis. In addition, the mRNA expression of hepcidin was also increased, suggesting blockage of iron recycling through FPN1 in spleen with cisplatin treatment. In conclusion, cisplatin treatment damages the erythrocytes which accumulate in the red pulp of spleen with defective recycling of FPN1 and ferritin protein. Hepcidin inhibits the function of FPN1 as iron-exporter leading to iron overloaded inside ferritins of splenic cells, which are stained with abnormal hemosiderin accumulation. These results demonstrate that cisplatin-caused hemosiderin deposition in spleen provides a valuable clue for understanding the molecular basis of toxicity of cisplatin and hemosiderin accumulation and iron metabolism in vivo.