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Post-radiofrequency ablation (RFA) fever is a self-limited complication of RFA. The correlation between post-RFA fever and bacteremia and the risk factors associated with post-RFA fever have not been evaluated. Patients with newly diagnosed or recurrent hepatocellular carcinoma who underwent ultrasonography-guided RFA between April 2014 and February 2019 were retrospectively enrolled. Post-RFA fever was defined as any episode of body temperature >38.0 °C after RFA during hospitalization. A total of 272 patients were enrolled, and there were 452 applications of RFA. The frequency of post-RFA fever was 18.4% (83/452), and 65.1% (54/83) of post-RFA fevers occurred on the first day after ablation. Patients with post-RFA fever had a longer hospital stay than those without (9.06 days vs. 5.50 days, p < 0.001). Only four (4.8%) patients with post-RFA fever had bacteremia. The independent factors associated with post-RFA fever were younger age (adjusted odds ratio (OR) = 0.96, 95% CI, 0.94-0.99, p = 0.019), low serum albumin level (adjusted OR = 0.49, 95% CI, 0.25-0.95, p = 0.036), general anesthesia (adjusted OR = 2.06, 95% CI, 1.15-3.69, p = 0.015), tumor size (adjusted OR = 1.52, 95% CI, 1.04-2.02, p = 0.032), and tumor number (adjusted OR = 1.71, 95% CI, 1.20-2.45, p = 0.003).

Background: Hepatocellular carcinoma (HCC) is one of the most common causes of cancer-related deaths worldwide. Particularly, cases of bone metastasis have poorer prognoses., Case Presentation: A 62-year-old woman with suspected advanced HCC accompanied by bone metastasis with severe back pain and sciatica showed disease remission after cyproheptadine monotherapy. Initially, her serum alpha fetal protein (AFP) level was high, reaching up to 17697.62 ng/ml. A dose of 4 mg cyproheptadine, 3 times a day for 17 months was prescribed as the only treatment. Within 3 months, the serum AFP level gradually normalized down to 4.3 ng/ml. Both liver biopsy and bone biopsies were subsequently performed after 2 weeks of cyproheptadine. The results showed no malignancy. During the 34 months of follow-ups, the serum AFP remained normal in the range of 1.05 to 2.86 ng/ml. The patient has survived for 5 years without back pain and sciatica thus far., Conclusions: This is the first report to investigate a successful clinical approach in cyproheptadine monotherapy for an advanced HCC patient with bone metastasis. We recommend cyproheptadine as a potential anti-HCC agent for the treatment of HCC with bone metastasis, but more related studies such as prospectively clinical trials, and ideally randomized trials are still needed., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The handling editor declared a shared affiliation with one of the authors DB at time of review., (Copyright © 2021 Feng, Chen, Berman, Chou, Liao, Hsieh and Chen.)

Plant viruses can be genetically modified to generate chimeric virus particles (CVPs) carrying heterologous peptides fused on the surface of coat protein (CP) subunits as vaccine candidates. However, some factors may be especially significant in determining the properties of chimeras. In this study, peptides from various sources and of various lengths were inserted into the Bamboo mosaic virus - based (BaMV) vector CP N-terminus to examine the chimeras infecting and accumulating in plants. Interestingly, it was found that the two different strains Foot - and - mouth disease virus (FMDV) VP1 antigens with flexible linker peptides (77 or 82 amino acids) were directly expressed on the BaMV CP, and the chimeric particles self - assembled and continued to express FMDV antigens. The chimeric CP, when directly fused with a large foreign protein (117 amino acids), can self-fold into incomplete virus particles or disks. The physicochemical properties of heterologus peptides N-terminus, complex strand structures of heterologus peptides C-terminus and different flexible linker peptides, can affect the chimera accumulation. Based on these findings, using plant virus - based chimeras to express foreign proteins can increase their length limitations, and engineered plant - made CVP - based vaccines have increasing potential for further development as novel vaccines.

Cyproheptadine, a serotonin antagonist, has recently been reported to function as a novel therapeutic agent by inhibiting PI3K/AKT signaling in several human cancers. However, the therapeutic effect of cyproheptadine in urothelial carcinoma (UC) has never been explored. In this study, we determined the effect of cyproheptadine on the growth of five human UC cell lines and an in vivo xenograft model. The results showed that cyproheptadine exerted an inhibitory effect on the proliferation of UC cells both in vitro and in vivo. Cyproheptadine also induced cell cycle arrest in the G1 phase, subsequently followed by apoptosis and necrosis. The underlying mechanisms of cell cycle arrest were associated with the reduction of c-Myc, induction of p21 and p27, and the stabilization of Rb expression. In addition, the suppression of the GSK3β/TSC2/mTOR pathway and deregulation of the GSK3β/β-catenin signaling were observed in cyproheptadine-treated UC cells. Furthermore, cyproheptadine-induced apoptosis was associated with ANGPTL4 expression followed by activation of caspase3 and PARP in UC cells. Our experimental results provide evidence that cyproheptadine is a suitable therapeutic agent for the treatment of UC., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)

Objective: Sorafenib is a recommended treatment for advanced hepatocellular carcinoma. The study is to evaluate the efficacy of sorafenib plus cyproheptadine compared with sorafenib alone in patients with advanced hepatocellular carcinoma., Methods: A retrospective cohort study reviewed all consecutive advanced hepatocellular carcinoma cases with Child-Pugh Class A disease starting sorafenib treatment at our hospital from August 2012 to March 2013. They were followed up until 31 December 2013. A total of 52 patients were enrolled: 32 patients in the combination (sorafenib-cyproheptadine) group and 20 patients in the control (sorafenib alone) group. The response to treatment, overall survival and progression-free survival were compared., Results: The median overall survival was 11.0 months (95% confidence interval: 6.8-15.1 months) in the combination group compared with 4.8 months (95% confidence interval: 3.1-6.6 months) in the control group (crude hazard ratio = 0.45, 95% confidence interval: 0.22-0.82). The median progression-free survival time was 7.5 months (95% confidence interval: 5.1-10.0 months) in the combination group compared with 1.7 months (95% confidence interval: 1.4-2.1 months) in the control group (crude hazard ratio = 0.43, 95% confidence interval: 0.22-0.86). Kaplan-Meier survival analysis revealed that both overall survival and progression-free survival in the combination group were significantly longer than that in the control group. The multivariate model found patients in the combination group were 76% less likely to die (adjusted hazard ratio = 0.24, 95% confidence interval: 0.10-0.58) and 82% less likely to have progression (adjusted hazard ratio = 0.18, 95% confidence interval: 0.08-0.44) during the 17 months of follow-up., Conclusion: Cyproheptadine may significantly improve survival outcomes of sorafenib-treated advanced hepatocellular carcinoma patients., (© The Author 2015. Published by Oxford University Press.)

Background: Hepatocellular carcinoma (HCC) is a major cause of cancer deaths worldwide. However, current chemotherapeutic drugs for HCC are either poorly effective or expensive, and treatment with these drugs has not led to satisfactory outcomes. In a 2012 case report, we described our breakthrough finding in two advanced HCC patients, of whom one achieved complete remission of liver tumors and the other a normalized α-fetoprotein level, along with complete remission of their lung metastases, after the concomitant use of thalidomide and cyproheptadine. We assumed the key factor in our effective therapy to be cyproheptadine. In this study, we investigated the antiproliferative effects and molecular mechanisms of cyproheptadine., Methods: The effect of cyproheptadine on cell proliferation was examined in human HCC cell lines HepG2 and Huh-7. Cell viability was assayed with Cell Counting Kit-8; cell cycle distribution was analyzed by flow cytometry. Mechanisms underlying cyproheptadine-induced cell cycle arrest were probed by western blot analysis., Results: Cyproheptadine had a potent inhibitory effect on the proliferation of HepG2 and Huh-7 cells but minimal toxicity in normal hepatocytes. Cyproheptadine induced cell cycle arrest in HepG2 cells in the G1 phase and in Huh-7 cells at the G1/S transition. The cyproheptadine-induced G1 arrest in HepG2 cells was associated with an increased expression of HBP1 and p16, whereas the G1/S arrest in Huh-7 cells was associated with an increase in p21 and p27 expression and a dramatic decrease in the phosphorylation of the retinoblastoma protein. Additionally, cyproheptadine elevated the percentage of Huh-7 cells in the sub-G1 population, increased annexin V staining for cell death, and raised the levels of PARP and its cleaved form, indicating induction of apoptosis. Finally, cyproheptadine-mediated cell cycle arrest was dependent upon the activation of p38 MAP kinase in HepG2 cells and the activation of both p38 MAP kinase and CHK2 in Huh-7 cells., Conclusions: Our results demonstrate that a non-classical p38 MAP kinase function, regulation of cell cycle checkpoints, is one of the underlying mechanisms promoted by cyproheptadine to suppress the proliferation of HCC cells. These results provide evidence for the drug's potential as a treatment option for liver cancer.

A 44-year-old woman suffered from epigastralgia for 1 month. An abdominal sonography revealed a space-occupying lesion, about 6 cm, in the spleen. Contrast-enhanced CT revealed enhanced splenic lesions. The PET/CT showed FDG-avid multiple splenic nodules with a "prunes on bread" appearance in the maximum-intensity-projection image (MIP image). In sectional PET/CT images, a central cold area with peripheral increased FDG uptake in the splenic nodule is visible. Because splenic malignancy was suspected, laparoscopic splenectomy was performed. Histology revealed multiple nodules with angiomatoid appearance, CD31(+), CD34(+) and HHV-8(-) in the vascular space, typical for the rare sclerosing angiomatoid nodular transformation (SANT).

We reported two cases of hepatocellular carcinoma (HCC) with lung metastases who were treated with a combination of thalidomide and cyproheptadine. The use of cyproheptadine in these two cases was originally for skin itching. Follow-up CT images revealed a complete remission of HCC in both of them after treatment for 6 months and 6 weeks, respectively. A following experimental cell line study demonstrated that cyproheptadine effectively reduced the viability of two HCC cell lines.