Objective To investigate immunological therapeutic effect and safety of dendritic cells (DCs) combined with heat shock protein 70 (HSP70)-peptide complex (PC) derived from autogeneic hepatoma tissue. Methods Thirty patients with hepatocellular carcinoma from February 2010 to February 2015 in the Gaochun People’s Hospital of Nanjing and The Third Affiliated Hospital of Nantong University were studied, and subsequently were divided into an immunotherapy group (treated with HSP70-PC/DCs vaccine,n=15) and a chemotherapy group (n=15) according to the prescribed postoperative treatment methods. The levels of T lymphocyte subtypes were assayed by FACS. The toxicity adverse reactions, alpha-fetoprotein (AFP), CA19-9, hepatic tumor recurrence rate, survival rate, and KPS of two groups patients were evaluated and compared between these two groups. Results ① The values of CD3+, CD4+, CD4+/CD8+, and CD3CD56 had no significant differences between the immunotherapy group and the chemotherapy group before treatment (P>0.05), which in the immunotherapy group were significantly higher than those in the chemotherapy group after treatment (P<0.05), and which were significantly higher in the immunotherapy group after treatment as compared with the levels before treatment (P<0.05), and which had no significant differences in the chemotherapy group between after treatment and before treatment (P>0.05). ② Before treatment, the levels of AFP and CA19-9 had no significant differences between the immunotherapy group and the chemotherapy group (P>0.05), which in the immunotherapy group were significantly lower than those in the chemotherapy group after treatment (P<0.05). In the immunotherapy group, the levels of AFP and CA19-9 after treatment were significantly lower than those before treatment (t=2.564，P=0.021；t=2.011，P=0.041), which in the chemotherapy group before treatment were decreased as compared with the levels before treatment (t=2.221,P=0.036;t=2.487,P=0.066). ③ The patients treated with the HSP-PC/DCs vaccines was well tolerated and no obvious toxicity was appeared. ④ All the patients were followed up 5–19 months with median follow-up time of 9 months. The median survival time was 560 d and 436 d in the immunotherapy group and the chemotherapy group, respectively. After treatment, KPS score was significantly higher and recurrence rate was significantly lower in the immunotherapy group as compared with the chemotherapy group (P<0.05). The total survival had no significant difference between the immunotherapy group and the chemotherapy group (P>0.05). Conclusions The preliminary results of limited cases in this study show that HSP70-PC/DC vaccination is safe and effective in treatment of hepatocellular carcinoma, the pulsed DCs are effective in activating specific T-cell responses against hepatocellular carcinoma cells. HSP70-PC/DC vaccine might improve immunity and prevent postoperative recurrence of hepatocellular carcinoma.
ObjectiveTo investigate the influencet of heat shock protein A2 (HSPA2) on the biological behavior of pancreatic adenocarcinoma cells and its mechanism. MethodsThe expression of HSPA2 in the human pancreatic adenocarcinoma cell lines PANC-1, BxPC-3, and AsPC-1 were determined using the Western blot analysis. The expression levels of heat shock protein A2 (HSPA2) were determined in human pancreatic cancer cell lines (PANC-1, BxPC-3, and AsPC-1) using Western blotting. Subsequently, the cells with the lowest and highest HSPA2 expression levels among these three lines were selected for conducting overexpression and knockdown experiments targeting HSPA2, respectively. The cellular proliferation, migration, and invasion capabilities were assessed using MTT, clonogenic, Transwell assays, respectively. Additionally, the impact of HSPA2 on the expression of key markers of epithelial-mesenchymal transition (EMT) was examined using the Western blot. The potential target molecules of HSPA2 were identified through immunoprecipitation assay and mass spectrometry. The rescue experiments further explored the regulatory relation between HSPA2 and its target molecules. The influence of HSPA2 on pancreatic adenocarcinoma growth was investigated through establishment of xenograft tumor model in nude mice.ResultsThe HSPA2 exhibited the lowest expression level in the PANC-1 cells and the highest expression level in the AsPC-1 cells among the three cell lines. Subsequent functional studies demonstrated that overexpression of HSPA2 in the PANC-1 cells significantly promoted proliferation, migration, and invasion, while knockdown of HSPA2 expression in the AsPC-1 cells markedly inhibited these processes. The Western blot analysis further showed that HSPA2 overexpression upregulated E-cadherin and downregulated N-cadherin/Vimentin, whereas HSPA2 knockdown produced opposite effects. The rescue experiments indicated that HSPA2 promoted the EMT in pancreatic adenocarcinoma cells by upregulating YAP. The subcutaneous xenograft tumor experiments in the nude mice showed that HSPA2 knockdown inhibited tumour growth. ConclusionThe results of this study suggest that HSPA2 promotes EMT via upregulating YAP, which facilitates proliferation, migration, and invasion of pancreatic adenocarcinoma cells.
ObjectiveTo explore the predictive value of preoperative serum heat shock protein 90α (HSP90α) level in combination with the prognostic nutritional index (PNI) for patients with hepatocellular carcinoma (HCC) after transarterial chemoembolization (TACE). MethodsThe HCC patients confirmed by histopathological examination and underwent TACE at Guigang People’s Hospital from January 2022 to June 2023 were as the observation group, the healthy individuals who underwent physical examinations during the same period and same hospital as the control group. The blood before treatment and on the day of the physical examination was collected to detected the HSP90α and albumin levels, as well as lymphocyte count. The PNI was calculated [PNI=albumin (g/L)+5×lymphocyte count (×109/L)]. The clinical outcome (tumor progression or death) was observed within one year after TACE treatment, those without tumor progression or death were defined as a good prognosis, while those with tumor progression or death were defined as a poor prognosis. Using the multivariate unconditional logistic regression analysis to identify the risk factors affecting the poor prognosis for HCC patients, and the receive operating characteristic (ROC) curve to evaluate the predictive value of serum HSP90α level in combination with PNI in distinguishing prognosis after TACE treatment.ResultsIn this study, there were 178 cases in the observation group and 100 cases in the control group. The serum HSP90α level (μg/L) in the observation group was higher than that in the control group (96.40±33.57 vs. 52.19±22.13, t=3.191, P<0.001), and the PNI value was lower than that in the control group (43.70±5.24 vs. 56.46±6.86, t=–16.144, P<0.001); Within one year after TACE treatment, there were 70 patients with poor prognosis and 108 patients with good prognosis. The serum HSP90α (μg/L) level in the patients with poor prognosis was higher than that in the patients with good prognosis (117.33±29.48 vs. 82.83±28.84, t=7.726, P<0.001), and the PNI was lower than that in the control group (40.49±4.18 vs. 45.78±4.80, t=–7.548, P<0.001). The multivariate unconditional logistic regression analysis found that the probabilities of incidence of poor prognosis after TACE treatment were higher in the patients with Chinese liver cancer staging Ⅲa–Ⅲb stage [reference: Ⅰ–Ⅱa stage, OR (95%CI)=5.332 (1.058, 26.875), P=0.043] and increased age and HSP90α level [OR (95%CI)=1.100 (1.025, 1.180), P=0.008; OR (95%CI)=1.049 (1.029, 1.070), P<0.001] , as well as decreased PNI value [OR (95%CI)=0.772 (0.686, 0.869), P<0.001]. The area under the ROC curve after TACE treatment in the HCC patients by serum HSP90α level in combination with PNI was 0.878 [95%CI=(0.820, 0.922)] in differentiating poor prognosis or not. ConclusionThe analysis results of this study suggest that preoperative serum HSP90α level in combination with PNI has a higher predictive value for prognosis of HCC patients after TACE treatment.