Massive bleeding from a gastric artery pseudoaneurysm in hepatocellular carcinoma treated with atezolizumab plus bevacizumab: A case report.

BACKGROUND: The combination of atezolizumab (ATZ) and bevacizumab (BVZ) was approved as first-line systemic therapy for advanced hepatocellular carcinoma (HCC) owing to its superior rates of response and patient survival. However, ATZ + BVZ is associated with increased risk of upper gastrointestinal (GI) bleeding, including arterial bleeding, which is rare and potentially fatal. We present a case of massive upper GI bleeding from a gastric pseudoaneurysm in a patient with advanced HCC who had been treated with ATZ + BVZ. CASE SUMMARY: A 67-year-old man presented with severe upper GI bleeding after atezolizumab (ATZ) + bevacizumab (BVZ) therapy for HCC. Endoscopy failed to detect the bleeding site. Digital subtraction angiography revealed a gastric artery pseudoaneurysm and contrast extravasation from the inferior splenic artery and a branch of the left gastric artery. Successful hemostasis was achieved with embolization. CONCLUSION: HCC patients who have been treated with ATZ + BVZ should be followed for 3 to 6 mo to monitor for development of massive GI bleeding. Diagnosis may require angiography. Embolization is an effective treatment.

[Preparation of 131I Labeled Collagen-Chitosan Microspheres and It's Antitumor Effect on Human Liver Cancer].

OBJECTIVE: To prepare iodine-131(131I) labeled biodegradable microspheres with chitosan and collagen for treating liver cancer. METHODS: Collagen-chitosan microspheres (CCMSs) were prepared with type-Ⅰ collagen and chitosan using emulsification-chemical cross-linking method. The size of the CCMSs were determined by electron microscope. 131I-CCMSs were achieved using Chloramine-T. The labelling rate of 131I was recorded. The stability of 131I-CCMSs in vitro were evaluated in PBS or human blood serum through 192 h incubation. The HepG2 model was established in nude mice 28 d after subcutaneous injection of 106 HepG2 cells. The model mice were sacrificed 7 d after injection of 131I-CCMSs,blank microspheres,or PBS (five mice in each group) into the HepG2 tumor xenografts. Samples of various organs were collected to determine the distribution of 131I-CCMSs. The curative effect of 131I-CCMSs on liver cancer was assessed by staining with HE for histological analyses. RESULTS: CCMSs were synthesized with a smooth and spherical shape and an average diameter of (5.1±1.2) µm. A radiolabeling rate of 86.10% was achieved. 131I radio-loading remained stable: 92.00% in saline and 83.00% in human serum after 192 h incubation. 131I was mainly concentrated in the subcutaneous tumor tissues. Potent curative effects of 131I-CCMSs on subcutaneous tumor tissues were demonstrated. CONCLUSION: Biodegradable CCMSs were successfully prepared and radiolabeled. The 131I-CCMSs exhibited potential curative effects on liver cancer,with high stability in vitro and in vivo.

[Establishment of Bone Metastasis Model of Prostate Cancer in Mice with Monitoring of 18F-NaF PET-CT].

OBJECTIVES: To establish a mouse model bearing human prostate cancer xenograft with bone metastasis by the monitoring with X-Ray, Micro CT, and ¹8F-NaF PET/CT. METHODS: Sixteen male Balb/c nude mice were allocated into control (6 mice) and experimental group (10 mice). In experimental group, the mice were subjected to percutaneous injection of 2×105PC-3 cells into tibial plateau, bone defects were assessed after 21 d by X-ray, Micro-CT and ¹8F-NaF PET/CT, and bone damages were evaluated by HE staining. In control group, equal volume of saline was injected into the mice. RESULTS: At 21 d post modeling, the significant radioactive ¹8F--NaF signals were found in the tibial intramedullary cavity of all 10 mice in experimental group. The ROI value evaluation showed that SUVmaxin control group was 0.62±0.14, but SUVmaxin tumor group was 2.10±0.13, which indicated abnormal bone metabolism. The serum alkaline phosphate level and HE staining results also confirmed that tumor mediated bone destruction and osteogenesis. However, X-ray and Micro-CT did not indicate precise diagnostic bone defect. CONCLUSION: Bone metastasis model of prostate PC-3 cancer cells were successfully established by intratibial injection. ¹8F-NaF PET/CT could detect tumor invasion and bone osteogenesis in the early stage of modeling.

[Cellular Uptake and Localization of Novel NSCLC Penetrating Peptide with Neuropilin-1 Binding Motif].

OBJECTIVE: To synthesize and study the specific binding affinity of tumor-penetrating peptide YCCS to non-small cell lung carcinoma (NSCLC) cells in vitro. METHODS: YCCS peptide was designed by fusing the neuropilin-1 (NRP-1) binding sequence and NSCLC binding peptide CS. YCCS peptide was synthesized and fluorescent labeled with N-terminal FITC. NRP-1 positive human NSCLC cell A549, NRP-1 positive human breast cancer cell MDA-MB-231, normal human bronchial epithelium HBE135-E6E7 and human liver cell HL-7702 were incubated respectively, then we observed the specific binding affinity of tumor-penetrating peptide YCCS to NSCLC cells. RESULTS: After treated with 5 µmol/L peptide, significant fluorescent signals of FITC-YCCS peptide were demonstrated only in NSCLC A549 cells but marginal captured signal in MDA-MB-231, normal human HBE135-E6E7 or HL-7702 cells, which revealed specific NSCLC cells binding affinity. In 20 µmol/L treated group, non-specific binding were found in MDA-MB-231 and HL-7702 cells. CONCLUSION: The results of this novel designed YCCS peptide indicated a promising strategy for improving tumor penetrating with delivery capability of drugs to NSCLC A549 cells when treated with 5 µmol/L peptide.