No abstract

The aim of the present study was to determine the clinical value of autologous immunocyte therapy as a standard treatment regimen for patients with cancer. A total of 121 patients with cancer were included in this study. Subsequent to performing leukapheresis using the Fresenius Kabi System, 1×107 dendritic cells (DCs) for the vaccine and 1×109 cytokine-induced killer (CIK) cells for injection were prepared. An analysis of the immune phenotypes of HLA2DR, CD80 and CD83 for the DCs and of CD3, CD8 and CD56 for the CIK cells, as well as negative detection of bacteria and endotoxin, were used as the quality standards. The delayed-type hyper-sensitivity (DTH) skin test was used to measure the immune response, while physical strength, appetite and sleeping status were analyzed for the clinical outcome. Fever, insomnia, anorexia, joint soreness and skin rashes were recorded as side-effects. Patients received the DC vaccination once a week for six weeks and a CIK cell injection six times within four days. In total, 121 cancer patients with primary tumors located in the colorectum (43.0%), lung (15.7%), breast (11.6%), kidney (5.8%), stomach (4.1%) and other regions (19.8%) were included in the study. A positive cell-mediated cytotoxicity response rate of 76.9% was detected by the DTH skin tests. Improvements in physical strength, appetite and sleeping status were observed in 94.1, 83.9 and 76.3% of cases, respectively. None of the serious adverse side-effects that commonly occur during chemotherapy and radiotherapy were observed. During therapy, 69 cases developed a fever that was resolved with antipyretics, dexamethasone or physical cooling, while 28 cases developed insomnia combined with excitement, 19 cases complained of anorexia, 11 cases complained of joint soreness, which was alleviated using analgesics, and 8 cases developed skin rashes. The combined use of CIK cells with a DC-based cancer vaccination strategy may be used to target innate and adaptive immune mechanisms and synergistically promote positive clinical outcomes. The therapy was safe and no serious adverse side-effects similar to those caused by chemotherapy and radiotherapy were observed. The regimen may have a beneficial effect in the future treatment of patients with cancer.

The study shows that it is possible to obtain typical DCs by culturing PBMCs from patients with IPAH with GM-CSF and IL-4, and it demonstrates that patients with IPAH have a significant change in the number of mDC and a marked immune deficiency of MoDCs.

BackgroundBortezomib, a proteasome-specific inhibitor, has emerged as a promising cancer therapeutic agent. However, development of resistance to bortezomib may pose a challenge to effective anticancer therapy. Therefore, characterization of cellular mechanisms involved in bortezomib resistance and development of effective strategies to overcome this resistance represent important steps in the advancement of bortezomib-mediated cancer therapy.ResultsThe present study reports the development of I-45-BTZ-R, a bortezomib-resistant cell line, from the bortezomib-sensitive mesothelioma cell line I-45. I-45-BTZ-R cells showed no cross-resistance to the chemotherapeutic drugs cisplatin, 5-fluorouracil, and doxorubicin. Moreover, the bortezomib-adapted I-45-BTZ-R cells had decreased growth kinemics and did not over express proteasome subunit β5 (PSMB5) as compared to parental I-45 cells. I-45-BTZ-R cells and parental I-45 cells showed similar inhibition of proteasome activity, but I-45-BTZ-R cells exhibited much less accumulation of ubiquitinated proteins following exposure to 40 nm bortezomib. Further studies revealed that relatively low doses of bortezomib did not induce an unfolded protein response (UPR) in the bortezomib-adapted cells, while higher doses induced UPR with concomitant cell death, as evidenced by higher expression of the mitochondrial chaperone protein Bip and the endoplasmic reticulum (ER) stress-related pro-apoptotic protein CHOP. In addition, bortezomib exposure did not induce the accumulation of the pro-apoptotic proteins p53, Mcl-1S, and noxa in the bortezomib-adapted cells.ConclusionThese results suggest that UPR evasion, together with reduced pro-apoptotic gene induction, accounts for bortezomib resistance in the bortezomib-adapted mesothelioma cell line I-45-BTZ-R.