Hepatocellular carcinoma (HCC) recurs frequently after minimally invasive therapy. The aim of our study was to observe the efficiency and safety of the combined treatment of radiofrequency ablation (RFA) with cellular immunotherapy (CIT) for HCC patients. In our study, 62 patients with HCC who were treated with radical RFA were divided into two groups: RFA alone (32 patients) and RFA/CIT (30 patients). Autologous mononuclear cells were collected from the peripheral blood and separated by apheresis, and then induced into natural killer (NK) cells, cdT cells and cytokine-induced killer (CIK) cells. These cells were identified by flow cytometry with their specific antibodies and then were infused intravenously to RFA/CIT patients for three or six courses. The tumor recurrent status of these patients was evaluated with computed tomography or magnetic resonance imaging every 3 months after RFA. Progression-free survival (PFS), liver function, viral load and adverse effects were examined. The results implied that PFS was higher in RFA/CIT group than that in RFA group. In RFA/CIT group, six courses had better survival prognosis than three courses. Viral load of hepatitis C was decreased in two of three patients without antiviral therapy in RFA/CIT group, but was increased in RFA group. No significant adverse reaction was found in the patients with CIT. In summary, these preliminary results suggest that combination of sequential CIT with RFA for HCC patients was efficient and safe, and may be helpful in the prevention of the recurrence for the patients with HCC after RFA.Hepatocellular carcinoma (HCC) is the fifth most common cancer and the third leading cause of cancer-related death worldwide. 1 Less than 30% of the patients can receive a curative therapy, such as surgery resection, local intervention therapy and transplantation. 2 For the majority of HCC cases, the prognosis is dismal owing to underlying cirrhosis as well as poor tumor response to chemotherapeutic agents. 3,4 Among the local therapy, radiofrequency ablation (RFA) treatment has been increasingly used for local ablation of liver tumors. 5,6 RFA has been proven to be a safe and efficient treatment for HCC. However, similar to other local therapies, the recurrence and metastasis after RFA remain a big issue in the patients with HCC. New therapeutic strategies are urgently needed to improve the therapeutic outcomes.The human immune system against the tumor is mainly dependent on the cellular immunity. Patients with HCC are found to have functional deficiency in a variety of immunocytes. 7-9 Thus, cellular immunotherapy (CIT) would improve the immune state to afford a potential value in enhancing the therapeutic outcome for HCC patients.Current attempts at harnessing the immune system to eliminate tumors have been focusing on vaccination such as dendritic cells (DCs) vaccine to increase the frequency of tumor-specific cytotoxic T lymphocytes (CTLs) and adoptive transfer of effector T cells to promote tumor regression. 10,11 However, despite considerable suc...
Background Acceleration of negative respiratory conversion of SARS-CoV-2 in patients with coronavirus disease 2019 (COVID-19) might reduce viral transmission. Nirmatrelvir/ritonavir is a new antiviral agent recently approved for treatment of COVID-19 that has the potential to facilitate negative conversion. Methods A cohort of hospitalized adult patients with mild-to-moderate COVID-19 who had a high-risk for progression to severe disease were studied. These patients presented with COVID-19 symptoms between March 5 and April 5, 2022. The time from positive to negative upper respiratory RT-PCR conversion was assessed by Kaplan-Meier plots and Cox proportional hazards regression with the adjustment for patients baseline demographic and clinical characteristics. Results There were 258 patients treated with nirmatrelvir/ritonavir and 224 non-treated patients who had mild-to-moderate COVID-19. The median (interquartile range) time for patients who converted from positive to negative RT-PCR was 10 days (7-12 days) in patients treated ≤5 days after symptom onset and 17 days (12-21 days) in non-treated patients, respectively. The proportions of patients with a negative conversion at day 15 were 89.7% and 42.0% in treated patients and non-treated patients, corresponding to a hazard ratio of 4.33 (95% CI, 3.31-5.65). Adjustment for baseline differences between the groups had little effect on the association. Subgroup analysis on treated patients suggests that time to negative conversion did not vary with the patients’ baseline characteristics. Conclusion This cohort study of high-risk patients with mild-to-moderate COVID-19 found an association between nirmatrelvir/ritonavir treatment and accelerated negative RT-PCR respiratory SARS-CoV-2 conversion that might reduce the risk of viral shedding and disease transmission.
ObjectivesHepatocellular carcinoma (HCC) is a leading cause of cancer-related deaths globally. In China, sorafenib and oxaliplatin plus infusional-fluorouracil/leucovorin (FOLFOX4) are approved for the systemic treatment of advanced HCC. This study compared the cost-effectiveness of these therapies from a healthcare system perspective and a patient perspectives.MethodsA Markov model was constructed using overall and progression-free survival rates and adverse event (AE) rate from two randomized controlled studies of advanced HCC patients from Asia: EACH for FOLFOX4 and ORIENTAL for sorafenib. The patients in the Markov model were followed until death, the length of each Markov cycle was 1 month, and the survival was adjusted for quality-adjusted life years (QALYs). Direct medical costs included costs of therapies, AE treatment, general ward and tests. Costs were derived from published sources, interviews with oncologists and hospital data from China. One-way and probabilistic sensitivity analyses (PSA) were performed to test the robustness of the results.ResultsFrom the healthcare system perspective, FOLFOX4 dominated sorafenib with lower therapy costs (FOLFOX4: US$ 6972; sorafenib: US$ 12,289), lower direct medical costs (FOLFOX4: US$ 8428; sorafenib: US$ 12,798), and higher QALYs (FOLFOX4: 0.42; sorafenib: 0.38) per patient. This result was robust according to comprehensive one-way sensitivity analyses. According to the PSA, at the cost-effectiveness threshold for China (3 × GDP, US$ 22,073), FOLFOX4 should be chosen in 63.9% of simulations. From the patient perspective, FOLFOX4 also dominated sorafenib.ConclusionsThe study results indicate that FOLFOX4 dominates sorafenib because it appears to provide higher effectiveness with significantly lower costs in treating Chinese advanced HCC patients.Electronic supplementary materialThe online version of this article (10.1186/s12962-018-0112-0) contains supplementary material, which is available to authorized users.
MicroRNA-874 (miR-874) is downregulated and acts as a tumor suppressor in several types of cancers, whereas the biological function of miR-874 in colorectal cancer (CRC) remains unclear. The aims of the present study were to investigate the clinical significance, biological effects, and the underlying mechanisms of miR-874 in CRC. Reverse transcription-quantitative PCR (RT-qPCR) was used to detect miR-874 expression in CRC cell lines and tissue samples. MTT and colony formation assays and flow cytometry were performed to analyze the effects of miR-874 expression on growth, apoptosis and the chemoresistance of CRC cells. Regulation of putative miR-874 targets was determined by dual-luciferase reporter assays. RT-qPCR and western blot assays were performed to detected the levels of X-linked inhibitor of apoptosis protein (XIAP) mRNA and protein expression. It was found that expression of miR-874 was downregulated in CRC tissues and cell lines, and its expression was significantly negatively correlated with TNM stage and lymph node metastasis of the CRC patients. Functional assays revealed that restoration of miR-874 inhibited proliferation, reduced colony formation, enhanced apoptosis, as well as decreased the 5-fluorouracil (5-FU) resistance of the CRC cells. Through luciferase activity assay, RT-qPCR and western blot analysis, XIAP was shown to be a direct target of miR-874. In addition, XIAP expression was significantly increased in the CRC tissues and cell lines, and was inversely correlated with miR-874 expression. Importantly, downregulation of XIAP in CRC cells had an effect similar to that of miR-874 overexpression. Taken together, these data showed that miR-874 inhibits growth, increases apoptosis and enhances chemosensitivity in CRC cells by targeting XIAP, suggesting that miR-874 may be a potential molecular target for the treatment of human CRC.
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