ABSTRACT
Photothermal therapy has been intensively investigated for treating cancer in recent years. However, the long-term therapeutic outcome remains unsatisfying due to the frequently occurred metastasis and recurrence. To address this challenge, immunotherapy has been combined with photothermal therapy to activate anti-tumor immunity and relieve the immunosuppressive microenvironment within tumor sites. Here, we engineered silica-based core‒shell nanoparticles (JQ-1@PSNs-R), in which silica cores were coated with the photothermal agent polydopamine, and a bromodomain-containing protein 4 (BRD4) inhibitor JQ-1 was loaded in the polydopamine layer to combine photothermal and immune therapy for tumor elimination. Importantly, to improve the therapeutic effect, we increased the surface roughness of the nanoparticles by hydrofluoric acid (HF) etching during the fabrication process, and found that the internalization of JQ-1@PSNs-R was significantly improved, leading to a strengthened photothermal killing effect as well as the increased intracellular delivery of JQ-1. In the animal studies, the multifunctional nanoparticles with rough surfaces effectively eradicated melanoma via photothermal therapy, successfully activated tumor-specific immune responses against residual tumor cells, and further prevented tumor metastasis and recurrence. Our results indicated that JQ-1@PSNs-R could serve as an innovative and effective strategy for combined cancer therapy.
ABSTRACT
Objective:To analyze the prognosis of patients with positive resection margin after radical prostatectomy, as well as the prostate-specific antigen (PSA)level and risk factors for PSA progression.Methods:A retrospective analysis was performed on the data of 141 patients with pathologically diagnosed prostate cancer who underwent RP from May 2012 to August 2020 in Beijing Hospital. The mean age was (67.4±6.7)years, the preoperative median PSA was 9.6 (1.4-152.8) ng/ ml and the median follow-up time was 56 months. Postoperative pathology was T 2 stage 74 (52.5%), T 3 stage 63 (44.7%), T 4 stage 4 (2.8%). Biochemical recurrence after radical resection was defined as PSA rose to more than 0.2 ng/ml and showed an upward trend after two consecutive follow-ups. In this study, serum PSA ≥ 0.1 ng/ml without biochemical recurrence after radical operation was defined as PSA progression. The PSA level, risk factors of PSA progression and prognosis of patients with positive resection margin were analyzed. Univariate and multivariate Cox regression analysis was used to analyze the correlation between age, preoperative PSA level, pathological stage (pT), ISUP classification, surgical approach, lymph node dissection, single/multiple positive margins and PSA progression. Results:The median follow-up of 141 patients was 52 months(1-104 months). There were 69 (48.9%) patients in the PSA progression group and 72 (51.1%) patients in the non PSA progression group. In the PSA progression group, 13 (18.8%) patients did not receive treatment and 8 (61.5%) patients had biochemical recurrence. 4 (5.8%) patients received radiotherapy alone, and 2 (50.0%) patients had biochemical recurrence. 52 (75.4%) patients received endocrine therapy or endocrine therapy combined with radiotherapy, and 5 (9.6%) patients developed castration resistance. Multivariate Cox regression analysis showed preoperative PSA ( HR=1.015, 95% CI 1.005-1.025, P =0.004), ISUP grade and group ( HR=1.351, 95% CI 1.091-1.673, P =0.006), surgical method ( HR=2.233, 95% CI 1.141-4.370, P =0.019) was correlated with PSA progression. Conclusions:The incidence of surgical positive margin is high after RP. Nearly half of the patients with surgical positive margin developed a PSA progression status. Preoperative PSA, ISUP grade group, and the surgical approach are risk factors for PSA progression in patients with positive surgical margins. Patients with these risk factors should be monitored more closely and treated more aggressively.
ABSTRACT
Objective To investigate the effect of lentivirus carrying shRNA-VDR vector on GLi1 in pros-tate cancer PC-3 cells. Methods The cells were cultured according to the culture conditions of PC-3 cells. Expression of VDR and GLi1 in PC-3 cells was detected by fluorescence quantitative PCR and immunocytochemistry SP method.The efficiency of PC-3 cell virus infection was evaluated.The effect of VDR gene interference and GLi1 transcription level on PC-3 cells was detected by RT-PCR.Results Cell culture,cell status was recorded and PC-3 cells were in good condition and the passages was 4 days. Fluorescence quantitative and immunocytochemi-cal SP showed that VDR and GLi1 were expressed in PC-3 cells.The virus infection efficiency showed that the in-fection efficiency was about 95% when adding LV3-NC lentivirus to PC-3 cells at 1:10 ratio. RT-PCR showed that VDR-shRNA lentivirus successfully disturbed VDR expression and decreased by 85%(P < 0.05)compared with the control group after 72 days of VDR-shRNA lentivirus transfection. Transcription level of GLi1 gene in the experimental group increased by 9% compared with the control group(P < 0.05). The transcription level of GLi1 gene in the experimental group increased by 248% compared with the control group(P < 0.05). Conclusion The cultured PC-3 cells were in good condition. VDR and GLi1 genes were expressed in PC-3 cells. Lentivirus showed highest efficiency in infecting PC-3 at 1:10 ratio. When VDR was disturbed,the expression of GLi1 in-creased.In prostate cancer cells,vitamin D can inhibit the Hh signaling pathway and cause GLi1 expression down expression.
ABSTRACT
Objective: To analyze the association between hepatitis B virus (HBV) infection and pancreatic cancer. Methods: Retrospective analysis was performed to explore the positive rate of serum hepatitis B virus surface antigen (HBsAg) in patients with pancreatic cancer, lung cancer, diabetes mellitus and general population. Z test was used to compare the rate of HBV infection between the samples and general population. The rates among the samples were compared by Chi-square test. Results: A total of 3,701 registered patients seen in our hospital between January 1st 2003 and March 31st 2009 were collected. There were 230 pancreatic cancer patients with a positive rate of serum HBsAg of 16.1%, 1,188 lung cancer patients with a positive rate of serum HBsAg of 10.7%, and 2,283 patients with diabetes mellitus with a positive rate of serum HBsAg of 11.6%. There was no statistical significance in Z-test results between lung cancer patients and general population (Z=1.104, P=0.163), but the Z-test results between patients with diabetes mellitus and general population showed a statistical significance (Z=2.98, P=0.002). The positive rate of HBsAg was higher in pancreatic cancer patients than that in lung cancer patients (OR=1.60, 95% Cl: 1.077-2.382, r=5.487, P=0.019). Similar results were found between pancreatic cancer patients and diabetic patients (OR=1.46, 95% CI: 1.004-2.123, r=3.965, P=0.046). Conclusion: The positive rate of HBsAg is high in pancreatic cancer patients. There might be an association between HBV infection and pancreatic cancer.