Case Report: Toripalimab Combined With Anlotinib in a Patient With Metastatic Upper Tract Urothelial Carcinoma After Pembrolizumab Failure.

Urothelial carcinoma is the most common primary upper tract urinary carcinoma. If surgery, chemotherapy, and immunotherapy fail, the prognosis for upper tract urinary carcinoma is extremely poor. Immunotherapy combined with antiangiogenesis therapy is a new therapeutic regimen with a synergistic antitumor effect. We present a case of metastatic upper tract urinary carcinoma in which the patient underwent surgery and treatment with gemcitabine combined with platinum-based chemotherapy. Radiotherapy and second-line immunotherapy (pembrolizumab) were administered after the cancer had progressed to the left lymph node of the abdominal aorta in the umbilical plane. However, the patient developed liver metastases while being treated with pembrolizumab. He was administered off-label immunotherapy (toripalimab) combined with antiangiogenesis therapy (anlotinib) and achieved a long-term clinical response for over 25 months. Toripalimab combined with anlotinib has potential therapeutic value for locally advanced or metastatic upper tract urinary carcinoma in patients who had previously received platinum-based chemotherapy and had disease progression or after treatment with a PD-1 inhibitor.

MiR-212 promotes proliferation and inhibits apoptosis of osteosarcoma cells via regulating hedgehog signaling pathway.

PURPOSE: To explore the effects of micro ribonucleic acid 212 (miR-212) on proliferation and apoptosis of osteosarcoma cells via the Hedgehog signaling pathway. METHODS: hFOB1.19 cells were enrolled as normal group, and osteosarcoma MG63 cells were divided into osteosarcoma group and miR-212 mimics group. The cells in the normal and osteosarcoma group were cultured normally, while those in miR-212 mimics group were cultured in medium containing miR-212 mimics. After 24 h of culture, the cells were collected for detection. Quantitative polymerase chain reaction (qPCR) assay was performed to determine the expression level of miR-212. The Gli1 expression level was measured by immunohistochemistry and Western blotting. Additionally, cell proliferation and apoptosis were detected by cell counting kit-8 (CCK-8) assay and flow cytometry, respectively. RESULTS: Based on immunohistochemistry, the average optical density of Gli1 positive expression was evidently increased in osteosarcoma group and miR-212 mimics group compared with that in normal group. The results of Western blotting and qRT-PCR showed that compared with those in normal group, the relative protein expression level of Gli1 and relative expression level of miR-212 were notably raised in the other two groups, and these levels were remarkably higher in miR-212 mimics group than those in osteosarcoma group. According to CCK-8 assay, the proliferation rate of cells was overtly higher in osteosarcoma group and miR-212 mimics group than that in normal group, and also distinctly higher in miR-212 mimics group than that in osteosarcoma group. CONCLUSIONS: MiR-212 promotes the proliferation and inhibits the apoptosis of osteosarcoma cells by up-regulating the Hedgehog signaling pathway.

Paclitaxel-loaded polymeric nanoparticles combined with chronomodulated chemotherapy on lung cancer: In vitro and in vivo evaluation.

The objective of our study was to examine the anti-tumor effect of paclitaxel (PTX)-loaded polymeric nanoparticles (PTX-NPs) combined with circadian chronomodulated chemotherapy. Our intention was to screen out the best time of the day for the drug to be administered. PTX-NPs with a diameter of approximately 168nm were prepared through a thin film dispersion technique. The PTX in PTX-NPs showed an initial fast release subsequently a slower and sustained release. The cytotoxicity of chronomodulated administration of PTX-NPs in vitro confirmed that its cytotoxic effect was lower than that of PTX injection, and showed a time-dependent effect. In addition, anti-tumor effect was examined by analysing tumor growth inhibition rate, micro-vessel density (MVD), cell proliferation and cell apoptosis, following either injection with PTX or administration of PTX-NPs. Micro fluorine-18-deoxyglucose PET/computed tomography (18F-FDG PET/CT) was used to evaluate tumor reactivity to PTX-NPs combined with chronomodulated chemotherapy. Taken these results into consideraion, our experiment indicates that PTX-NPs exhibit greater anti-tumor activity against A549 cells, in comparison with PTX injection, and the anti-tumor effect at 15h after light onset (HALO) administration is the best in all groups. Therefore, prepared PTX-NPs combined with chronomodulated chemotherapy could be a potential treatment for lung cancer.