BackgroundRecently, increased tumor incidence and cancer-related mortality have been reported among patients with obstructive sleep apnea (OSA). Intermittent hypoxia (IH), the hallmark feature of OSA, contributes to the metastasis of tumors. However, the molecular mechanisms by which tumor metastasis is accelerated by OSA-like IH remain to be elucidated.MethodsC57BL/6 J male mice were subjected to intravenous injection of B16F10 melanoma cells before receiving IH treatment. Then, the animals were randomly distributed into three groups (n = 8 each): normoxia (N) group, IH group, and antioxidant tempol group (IHT, exposed to IH after treatment with tempol). After the mice were sacrificed, the number and weight of lung metastatic colonies were assessed. The lung tissues with tumor metastasis were analyzed for markers of oxidative stress and inflammation and for HIF-1α using western blotting and real-time PCR (qRT-PCR). The level of reactive oxygen species (ROS) in B16F10 cell was also assessed after N, IH and IH with tempol treatments.ResultsCompared with normoxia, IH significantly increased the number and weight of mouse lung metastatic colonies. Treatment of B16F10 cells with IH significantly enhanced ROS generation. Lung tissues with tumor metastasis provided evidence of increased oxidative stress, as assessed by p22phox and SOD mRNA levels and the NRF2 protein level, as well as increased inflammation, as assessed by TNF-α and IL-6 mRNA levels and the NF-κB P65 protein level. HIF-1α protein levels were increased in response to IH treatment. Tempol, an important antioxidant, ameliorated IH-induced melanoma lung metastasis in mice and reduced oxidative stress and inflammation responses.ConclusionsThese results support the hypothesis that oxidative stress and inflammation responses play an important role in the pathogenesis of OSA-like IH-induced melanoma lung metastasis in mice. Antioxidant intervention provides a novel strategy for the prevention and treatment of cancer in OSA populations.

Combination of a variety of imaging modalities could more fully reflect the pathological characteristics and contribute to the diagnosis of SH.

The practical application of genistein as a low toxicity chemotherapeutic drug is hindered by many of its in vivo properties. To overcome these obstacles, a new multifunctional drug delivery system is developed, which is based on covalently attaching genistein onto Fe3O4 nanoparticles coated by cross-linked carboxymethylated chitosan (CMCH). The structure of the Fe3O4-CMCH-genistein nano-conjugate was confirmed by transmission electron micrographs (TEM), X-ray diffraction (XRD) and Fourier-transfer infrared (FT-IR) spectroscopy. The nano-conjugate shows good water solubility and superparamagnetic properties with a saturation magnetization of 55.1 emu/g. The effects of free genistein and FeO4-CMCH-genistein nano-conjugate on the proliferation and apoptosis of gastric cancer cell line SGC-7901 were investigated by MTT assay and flow cytometry (FACS). MTT results indicate that the Fe3O4-CMCH-genistein nano-conjugate exhibits a significantly enhanced inhibition effect to the SGC-7901 cancer cells than the free genistein. FACS data suggests that the inhibition on cell proliferation of the nano-conjugate is related with an induced apoptosis process. This drug delivery system is promising for future multifunctional chemotherapeutic application that combines drug release and magnetic hyperthermia therapy.

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AIM:To explore the feasibility of computed tomography (CT)-guided percutaneous ethanol injection (PEI) using a disposable curved needle for treatment of malignant liver neoplasms and their metastases in retroperitoneal lymph nodes. METHODS:CT-guided PEI was conducted using a disposable curved needle in 26 malignant liver tumors smaller than 5 cm in diameter and 5 lymph node metastases of liver cancer in the retroperitoneal space. The disposable curved needle was composed of a straight trocar (21G) and stylet, a disposable curved tip (25 G) and a fine stylet. For the tumors found in deep sites and difficult to reach, or for hepatic masses inaccessible to the injection using a straight needle because of portal vein and bile ducts, the straight trocar was used at first to reach the side of the tumor. Then, the disposable curved needle was used via the trocar. When the needle reached the tumor center, appropriate amount of ethanol was injected. For relatively large malignant liver tumors, multi-point injection was carried out for a better distribution of the ethanol injected throughout the masses. The curved needle was also used for treatment of the metastasis in retroperitoneal lymph nodes blocked by blood vessels and inaccessible by the straight needle. RESULTS:All of the 26 liver tumors received 2 or more times of successful PEI, through which ethanol was distributed throughout the whole tumor mass. Effect of the treatment was monitored by contrast-enhanced multi-phase CT and magnetic resonance imaging (MRI) examinations three months later. Of the 18 lesions whose diameters were smaller than 3 cm, the necrotic change across the whole mass and that in most areas were observed in 15 and 3 tumors, respectively. Among the 8 tumors sizing up to 5 cm, 5 were completely necrotic and 3 largely necrotic. Levels of tumor seromarkers were significantly reduced in some of the cases. In 5 patients with metastases of liver cancer in retroperitoneal lymph nodes who received 1 to 3 times of PEI, all the foci treated were completely necrotic and smaller demonstrated by dynamic contrast-enhanced CT or MRI 3 months later.CONCLUSION: CT-guided PEI using a disposable curved needle is effective, time-saving and convenient, providing an alternative therapy for the treatment of malignant liver tumors and their retroperitoneal lymph node metastases.Zuo CJ, Wang PJ, Shao CW, Wang MJ, Tian JM, Xiao Y, Ren FY, Hao XY, Yuan M. CT-guided percutaneous ethanol injection with disposable curved needle for treatment of malignant liver neoplasms and their metastases in retroperitoneal lymph nodes.