MicroRNA let-7d targets thrombospondin-1 and inhibits the activation of human pancreatic stellate cells

博士（医学）福島県立医科大

Drug treatment for chemotherapy-induced peripheral neuropathy in patients with pancreatic cancer

Pancreatic cancer (PC) is a lethal disease where most tumors are too advanced at diagnosis for resection, leaving chemotherapy as the mainstay of treatment. Although the prognosis of unresectable PC is poor, it has been dramatically improved by new chemotherapy treatments, such as the combination of 5-fluorouracil, oxaliplatin, irinotecan, and leucovorin (FOLFIRINOX) or gemcitabine plus nab-paclitaxel. However, as oxaliplatin and paclitaxel are common neurotoxic drugs, chemotherapy-induced peripheral neuropathy (CIPN) is a common and severe adverse effect of both treatments. As there are no agents recommended in the ASCO guidelines, we review the methods used to treat CIPN caused by PC treatment. The efficacy of duloxetine was observed in a large randomized controlled trial (RCT). In addition, pregabalin was more effective than duloxetine for CIPN in two RCTs. Although duloxetine and pregabalin can be effective for CIPN, they have several side effects. Therefore, the choice between the two drugs should be determined according to effect and tolerability. Mirogabalin is also used in patients with PC and there is hope it will yield positive outcomes when treating CIPN in the future

Polaprezinc prevents ongoing thioacetamide-induced liver fibrosis in rats.

AuthorAims: Cirrhotic patients commonly have a liver zinc deficiency, which may aggravate liver fibrosis due to the lack of antioxidative effects of zinc. This study examined the ability of polaprezinc, N-(3-aminopropionyl)-Lhistidinato zinc, to prevent fibrosis in a rat model of thioacetamide (TAA)-induced hepatic fibrosis. Main methods: Liver cirrhosis was induced by orally administering TAA for 20 weeks. The rats were cotreated with one of the following for the last 10 weeks of TAA treatment: (1) polaprezinc (50 or 200 mg/kg/day); (2) L-carnosine (155 mg/kg/day),which contained equal amounts of L-carnosine as 200 mg/kg/day polaprezinc; (3) zinc sulfate (112 mg/kg/day) or (4) zinc-L-aspartic complex (317.8 mg/kg/day). Both zinc supplementations contained equal amounts of zinc as high-dose polaprezinc. Key findings: Hepatic zinc levels fell significantly in rats treated with TAA for 20 weeks. Cotreating with high-dose polaprezinc and zinc-L-aspartic complex for 10 weeks prevented hepatic zinc loss. Hepatic hydroxyproline and tissue inhibitor of metalloproteinases-1 (TIMP-1) were significantly higher in rats treated with TAA for 20 weeks than 10 weeks, whereas polaprezinc prevented changes in these fibrosis markers and reduced hepatic transforming growth factor-β1 protein concentration, macroscopic and histologic changes. TAA caused oxidative stress-related changes in the liver that were prevented by high-dose polaprezinc and partially by zinc-L-aspartic complex. Treatment with L-carnosine, low-dose polaprezinc or zinc sulfate for 10 weeks did not affect liver fibrosis progression or oxidative stress-related changes. Significance: Polaprezincmay prevent ongoing fibrosis by preventing zinc depletion, oxidative stress and fibrosis markers in cirrhotic livers