Renal Abscess Caused by Crizotinib: A Rare Case Report.

Crizotinib is a tyrosine kinase inhibitor that has been found to be effective in the treatment of c-ros oncogene 1-positive non-small cell lung cancer. Although this targeted agent for treating cancer has shown superiority to standard chemotherapy in some ways, this drug has adverse effects, such as the development of renal abscesses. Some associated renal damage may disappear with crizotinib withdrawal. Hence, we present the case of a 58-year-old man with non-small cell lung cancer on crizotinib therapy who developed bilateral renal abnormal space-occupying lesions, successively which were difficult to identify using various imaging methods; even PET-CT highly suspected the right renal masses as malignant. Finally, the right renal lesions were confirmed as renal abscesses by postoperative pathology. The left renal lesion was considered as renal cysts through the lesion disappearing after crizotinib withdrawal. There have been very few reports in this respect, especially proved by various methods and confirmed by postoperative pathology. It is important to recognize this drug-related complication in order to avoid incorrect diagnosis and inadequate therapy. It is necessary to monitor renal changes after taking crizotinib.

To evaluate the efficacy and safety of 125I seed implantation in SCLC as second line therapy.

This study aimed to evaluate the efficacy and safety of iodine 125 (125I) radioactive seed implantation for small cell lung cancer at the limited stage of relapse as second line therapy. We collected 6 patients with recurred limited stage small cell lung cancer, who got pathological diagnosis after a bronchoscopic biopsy and then received standard first line treatment, combined chemotherapy and radiotherapy, including prophylactic cranial irradiation. These recurred small cell lung cancer patients got 125I seed implantation treatment as second line therapy, if the treatment not good responsive or the disease got rapid progress, we used the second line chemotherapy as salvage treatment. Clinical data of these patients were collected and short-term effects were observed. The follow-up period lasted for 42 months. All the patients tolerated the procedure of 125I radioactive seed implantation very well. We followed up the patients to 42 months. Five patients got complete remission and 1 patient got partial remission at 1 month after implantation. The objective response rate was 100%. The median survival time was 26 months. And median progression-free survival was 12 months after 125I treatment. And about the complications, 1 patient suffered from the light aerothorax, 1 patient had a little hemoptysis. Our study showed that 125I seed implantation as second line regimen in small cell lung cancer that recurred locally after first line treatment was effective and safe. That could improve the overall survival and progression-free survival only comparing to the second line chemotherapy. Therefore 125I seed implantation as brachytherapy protocol is a promising method and can be applied as second line treatment to control the locally recurred small cell lung cancer.

Downregulation of SNAIL sensitizes hepatocellular carcinoma cells to TRAIL-induced apoptosis by regulating the NF-κB pathway.

Hepatocellular carcinoma (HCC) is the sixth most common cancer and the second most lethal cancer worldwide. Evidence has shown HCC cell resistance to TRAIL­mediated apoptosis. In a previous study, we verified that silencing SNAIL downregulated the growth of HCC cells. In addition, the mechanism of resistance to TRAIL in HCC cells was connected with the activation of nuclear factor-κB (NF-κB). Thus, it was hypothesized that the downregultaion of SNAIL sensitizes HCC cells to TRAIL-induced apoptosis by regulating the NF-κB pathway. In the present study, the most effective lentiviral vectors carrying shRNA against SNAIL were selected and adenoviral vectors harboring TRAIL were constructed. The expression of SNAIL and TRAIL was detected by quantitative PCR and western blotting. HCC cell viability and apoptosis were assessed using an MTT assay and the Hoechst test. To determine how to sensitize HCC cells to TRAIL-induced apoptosis after silencing SNAIL, p53 was assessed by western blot analysis. We also investigated the expression of Bcl-xL, cIAP2, survivin and Raf-1 protein using western blot analysis and the apoptotic degree of HuH-7 cells was detected using the Hoechst test following the suppression of each gene, which was a possible molecular mechanism to sensitive TRAIL-induced apoptosis through the downregulation of SNAIL in HCC cells. Silencing SNAIL resulted in increased apoptosis by enhancing sensitization to TRAIL in all the HCC cells. Additionally, p53 protein was upregulated in HuH-7 cells. Expression of Bcl-xL, cIAP2, survivin and Raf-1 was downregulated following silencing of SNAIL, while down-regulation of any of the proteins contributed to SNAIL suppression enhancing HCC cell sensitivity to TRAIL­induced apoptosis, with the exception of cIAP2. The results demonstrated that silencing SNAIL can sensitize TRAIL-induced apoptosis in HCC cells by upregulating p53 protein and by regulating related genes of the NF-κB pathway such as Bcl-xL, survivin and Raf-1.

Glycogen synthase kinase-3ß regulates tumor necrosis factor-related apoptosis inducing ligand (TRAIL)-induced apoptosis via the NF-κB pathway in hepatocellular carcinoma.

Tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) is known for its ability to selectively induce apoptosis in malignant cells. However, human hepatocellular carcinoma (HCC) cells display resistance to TRAIL-induced cell death. The present study investigated whether TRAIL-induced apoptosis in HCC cells was enhanced by the administration of an inhibitor of glycogen synthase kinase-3ß (GSK-3ß) or by short hairpin RNA-mediated inhibition of GSK-3ß. The results of the current study demonstrated that inhibition of GSK-3ß significantly impairs the expression of the nuclear factor-κB (NF-κB) target genes Bcl-xL and clAP2 in HCC cells (P<0.05). This indicates that GSK-3ß may regulate NF-κB target genes involved in cell survival. Furthermore, knockdown of Bcl-xL significantly enhanced the sensitizing effect of GSK-3ß inhibitor on TRAIL-induced apoptosis (P<0.05). Overall, the present study provides a rationale for further exploration of GSK-3ß inhibition combined with TRAIL as a novel treatment for HCC.

[Clinical application of prefilled pen and conventional syringe during controlled ovarian stimulation for in vitro fertilization].

OBJECTIVE: To investigate the efficacy, convenience and costs of recombinant follitropin alpha administered by a prefilled pen device and conventional syringe in Chinese women undergoing controlled ovarian stimulation for in vitro fertilization (IVF). METHODS: A total of 184 patients undergoing IVF treatment were enrolled in this study. According to a long-term recombinant follicle-stimulating hormone (rFSH) protocol, ovarian stimulation was performed with the prefilled pen and conventional syringe at random in these subjects, and the dose of follitropin, number of oocytes and embryo parameters and IVF-ET outcome were compared between the two groups. RESULTS: The total rFSH dose, cost, and frequency of hospital visits were significantly lower in the pen protocol group, but the residual rFSH amount was higher. Compared with conventional injections, the prefilled pen was associated with significantly lowered rate of local redness, high rate of local bruise, more frequent follitropin dose modulation and lower serum oestradiol levels on HCG day. No significant difference was found in the endometrial thickness, numbers of oocytes retrieved, MII oocytes, transferred embryo, or the clinical pregnancy rates between the two groups. The ratio of MII oocytes, good quality embryo rates and implantation rates was significantly higher in the pen group with lower incidences of moderate and severe ovarian hyperstimulation syndrome. CONCLUSION: The prefilled pen provides an easy, safe, effective and more patient-friendly means for controlled ovarian stimulation procedure in Chinese women, but more attention should be given to protocol optimization and patient education.