Objective
To investigate the application of molecular absorbent recycling system (MARS) in auto liver transplantation (ALT).
Methods
The clinical data of 46 patients who underwent ALT in Zhongnan Hospital of Wuhan University from September 2014 to August 2015 were retrospectively studied. The patients were randomly divided into the MARS group (n=30) and the hemodialysis group (n=16). In the MARS group, 20 patients were male and 10 were female with an average age of (15±67) years, and the median age was 46. In the hemodialysis group, 8 were male and 8 were female with an average age of (22±54) years. A heparinized left iliac vein was linked to a centrifugal pump of a MARS and an output tube was linked to a left jugular vein. Before the anhepatic phase, physical pretreatment was carried out by ligating the porta hepatis and inferior vena cava (IVC) to adapt the patient to the anhepatic phase. Subsequently, a bypass was established followed by ligation of the IVC. The duration of operation, length of stay in ICU after operation, one-year survival rate and hepatorenal function were studied.
Results
The duration of operation in the MRAS group and in the hemodialysis group was not significantly different (P>0.05). The length of stay in ICU after operation in the MARS group was (12.0±3.0) d, which was significantly shorter than that of the hemodialysis group (20.0±2.0) d (P<0.05). The one-year survival rate in the MARS group was (100%), which was significantly higher than that of the hemodialysis group (93.8%, P<0.05).
Conclusion
The application of MARS in ALT shortened the length of stay in hospital and improved one-year survival rate, resulting in better outcomes than the conventional method.
Key words:
Molecular absorbent recycling system; Auto liver transplantation; Comparative study
Pancreatic ductal adenocarcinoma (PDAC) is a malignant tumor with insidious onset, rapid progression, and a very poor prognosis. CD47 is a transmembrane protein associated with the development and poor prognosis of pancreatic cancer. The aim of this study was to evaluate the diagnostic value of novel immunoPET tracers targeting CD47 in preclinical pancreatic cancer models. The association of CD47 expression with pancreatic cancer was analyzed using the Gene Expression Profiling Interactive Analysis platform. Immunohistochemical analysis of tissue microarrays was performed to detect CD47 expression in PDAC. CD47 expression levels on BxPC-3 and AsPC-1 cell membranes were compared using flow cytometry. A VHH (C2)-targeting human CD47 and its albumin-binding derivative (ABDC2) were labeled with 68Ga or 89Zr, respectively. The developed tracers were evaluated by immuno-positron emission tomography (immunoPET) imaging in tumor-bearing nude and CD47-humanized mice. [68Ga]Ga-NOTA-C2 effectively detected tumor lesions in nude mice models and further showed confirmative imaging capacity in CD47-humanized PDAC models. Compared with [68Ga]Ga-NOTA-C2, [89Zr]Zr-DFO-ABDC2 had a significantly prolonged circulation time, increased tumor uptake, and reduced accumulation in the kidneys. Finally, biodistribution and histological staining confirmed the results of the immunoPET imaging studies. In this study, we validated that two novel VHH-derived molecular imaging tracers for immunoPET imaging ([68Ga]Ga-NOTA-C2 and [89Zr]Zr-DFO-ABDC2) can effectively annotate CD47 expression and diagnose PDAC in a target-specific manner. Clinical application of the imaging strategies may help select patients for CD47-targeted therapies and assess the response thereafter.
Unresolved inflammation, due to insufficient production of proresolving anti-inflammatory lipid mediators, can lead to tumorigenesis. Among these mediators, lipoxin A4 (LXA4) has potent anti-carcinogenic properties, and may serve as key target for modulating inflammation-associated cancer like colorectal cancer. The purpose of present study was to clarify the roles of LXA4 in colorectal cancer. We investigated the effects and underlying mechanisms of LXA4 in colorectal cancer and its relationship with tumor-associated inflammation and immune microenvironment by employing clinical samples and mouse colorectal cancer cell line CT26-bearing tumor model as well as colorectal cancer cells. It was found that colorectal cancer is associated with dysregulation of immune microenvironment and deficiency of LXA4 that could play different roles at different stages of tumor growth: inhibiting early but promoting late tumor growth. Analysis of peripheral immune cells in subcutaneous xenograft mice model disclosed that early LXA4 treatment induced lymphocytes and inhibited neutrophils and monocytes, while late LXA4 treatment induced neutrophils but inhibited lymphocytes. Detailed analysis of tumor microenvironment revealed that early LXA4 treatment could inhibit inflammatory mediators expressions and leukocytes infiltration into tumor. Furthermore, LXA4 could suppress the expressions of p-ERK, p-P38 and NF-κB in subcutaneous xenograft. Additionally, LXA4 could inhibit the proliferation and migration of colorectal cancer cells, and, meanwhile, inhibit the proliferation and migration of colorectal cancer cells stimulated by activated macrophage-conditioned media. These findings suggest that colorectal cancer is associated with a deficiency of LXA4 that could suppress colorectal cancer via modulating tumor-associated inflammation and immune microenvironment as well as inhibiting colorectal cancer cell development.
Objective: To analyze the clinical and biological significance of the acute promyelocytic leukemia (APL) whose PML-RARa transcripts increased after induction therapy.Methods: We analyzed 9 cases of APL whose PML-RARa transcripts increased after induction treatment and compare them with APL whose PML-RARa transcripts decreased.Results: The only factor affecting increased PML-RARa transcripts was the induction protocol. The cases of increased PML-RARa transcripts received induction treatment mainly based on ATRA and ATO. The evaluation of bone marrow aspirate cytology showed that the cell percentage from myelocyte to segmented neutrophil of the patients with increased PML-RARa transcripts was significantly higher than that of the patients with decreased PML-RARa transcripts. In the follow-up, MRD in 9 cases was consistently negative.Conclusions: Our studies showed the increased PML-RARa transcripts after induction treatment had different clinical significance from the decreased PML-RARa transcripts.
Hypoxia is a fundamental hallmark of solid tumors and helps contribute to chemotherapy resistance. Hyperbaric oxygen (HBO) therapy can overcome tumor hypoxia and promote chemotherapy antitumor efficacy; however, the simultaneous administration of some conventional chemotherapies, including doxorubicin (DOX), with HBO is considered an absolute contraindication. Here, DOX-loaded liposome (Doxil) is coadministered with HBO to assess the safety and efficacy of this combination treatment. By overcoming tumor hypoxia, HBO not only improves Doxil tumor penetration by decreasing the collagen deposition but also sensitizes tumor cells to Doxil. As a result, the combination treatment synergistically inhibits H22 tumor growth, with a tumor inhibition rate of 91.5%. The combination of HBO with Doxil shows neither extra side effects nor promotion of tumor metastasis. These results collectively reveal that the combination of HBO with Doxil is an effective and safe treatment modality. As both HBO and Doxil are routinely used, their combination could quickly translate to clinical trials for patients with hypoxic solid tumors.
B-cell lymphoma-extra large (Bcl-xL), an important member of anti-apoptotic Bcl-2 family, is involved in tumor progression and development. The overexpression of Bcl-xL is associated with radioresistance of human malignancies. The present study aimed to investigate the inhibitory effect of small interfering RNA (siRNA) on the expression of Bcl-xL in the A549 non-small lung cancer (NSCLC) cell line, and its role in inducing the apoptosis and increasing the radiosensitivity of A549 cells. An siRNA expression vector, pSilencer4-CMVneo-short hairpin (sh)RNA, was constructed and stably transfected into A549 cells. The effects of Bcl-xL-shRNA on cell proliferation, apoptosis and the protein expression levels of associated proteins were assessed in vitro in the A549 cells. The radiosensitivity of the A549 cells was evaluated using a clonogenic cell survival assay. The results demonstrated that the sequence-specific siRNA targeting Bcl-xL efficiently and specifically downregulated the mRNA and protein expression levels of Bcl-xL. The RNA interference-mediated downregulation in the expression of Bcl-xL inhibited cell proliferation, induced apoptosis and reduced the radioresistance of the NSCLC cells. These findings suggested that Bcl-xL may be a promising therapeutic approach for the treatment of NSCLC.
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